Features Of Acute Lymphoblastic Leukemia Research Articles

Chromosomal Variations and Clinical Features of Acute Lymphoblastic Leukemia in the North Indian Population: A Cross-Sectional Study.

The key prognostic markers in acute lymphoblastic leukemia (ALL) include age, leukocyte count upon diagnosis, immunophenotype, and chromosomal abnormalities. Furthermore, there was a correlation between cytogenetic anomalies and specific immunologic phenotypes of ALL, which in turn had varied outcomes. The objective of this study was to examine the occurrence of cytogenetic abnormalities in individuals diagnosed with acute lymphoblastic leukemia. The study employed a cross-sectional design to investigate genetic evaluation and clinical features in 147 ALL patients between March 2021 and August 2022. Demographic data (like age and sex), clinical manifestations, and hematological parameters were collected. Cytogenetic analysis (G-banding) was performed to identify chromosomal abnormalities. The mean±SD and analysis of variance (ANOVA) were usedtoassess associations and differences among variables usingSPSS Version 24 (IBM Corp., Armonk, NY, USA). The study shows male n=85 andfemale n=62 in ALL patients, with prevalent clinical manifestations: fever n=100 (68.03%), pallor n=123 (83.67%), and lymphadenopathy n=65 (44.22%).Thehematologicalparameters like hemoglobin (Hb) (6.14±2.5 g/dl),total leukocyte count (TLC)(1.7±1.05 cell/mm3), and platelet count (1.2±0.11 lac/mm3) show a significant variation (P<0.05) in patients aged 30-50 years.In addition,chromosomal abnormalities, particularly 46, XX, t(9;22), were prevalent, emphasizing the genetic heterogeneity of ALL. The study shows a male predominance with ALL, prevalent clinical manifestations, and significant hematological parameter variations in the 30-50 age group. Chromosomal abnormalities, notably 46, XX, t(9;22), underscore the genetic complexity of the disease, which necessitates tailored therapeutic interventions informed by genetic profiles.

Design and Validation of a Custom Next-Generation Sequencing Panel in Pediatric Acute Lymphoblastic Leukemia.

The molecular landscape of acute lymphoblastic leukemia (ALL) is highly heterogeneous, and genetic lesions are clinically relevant for diagnosis, risk stratification, and treatment guidance. Next-generation sequencing (NGS) has become an essential tool for clinical laboratories, where disease-targeted panels are able to capture the most relevant alterations in a cost-effective and fast way. However, comprehensive ALL panels assessing all relevant alterations are scarce. Here, we design and validate an NGS panel including single-nucleotide variants (SNVs), insertion-deletions (indels), copy number variations (CNVs), fusions, and gene expression (ALLseq). ALLseq sequencing metrics were acceptable for clinical use and showed 100% sensitivity and specificity for virtually all types of alterations. The limit of detection was established at a 2% variant allele frequency for SNVs and indels, and at a 0.5 copy number ratio for CNVs. Overall, ALLseq is able to provide clinically relevant information to more than 83% of pediatric patients, making it an attractive tool for the molecular characterization of ALL in clinical settings.

Quantifying imbalanced classification methods for leukemia detection

Uncontrolled proliferation of B-lymphoblast cells is a common characterization of Acute Lymphoblastic Leukemia (ALL). B-lymphoblasts are found in large numbers in peripheral blood in malignant cases. Early detection of the cell in bone marrow is essential as the disease progresses rapidly if left untreated. However, automated classification of the cell is challenging, owing to its fine-grained variability with B-lymphoid precursor cells and imbalanced data points. Deep learning algorithms demonstrate potential for such fine-grained classification as well as suffer from the imbalanced class problem. In this paper, we explore different deep learning-based State-Of-The-Art (SOTA) approaches to tackle imbalanced classification problems. Our experiment includes input, GAN (Generative Adversarial Networks), and loss-based methods to mitigate the issue of imbalanced class on the challenging C-NMC and ALLIDB-2 dataset for leukemia detection. We have shown empirical evidence that loss-based methods outperform GAN-based and input-based methods in imbalanced classification scenarios.

ALL-350 Characterization of Acute Lymphoblastic Leukemia in the Pediatric Mexican Mestizo Population

Acute lymphoblastic leukemia (ALL) is the most common neoplasm of lymphoid progenitor cells in pediatric populations. ALL cases can be broadly classified as B-cell or T-cell. B-cell ALL (B-ALL) has many genetic subtypes characterized by major chromosomal alterations. Flow cytometry and biomarkers identification provide information about the subtype of ALL and can be correlated with the patient's prognosis. Based on reactivity with antigens present on the surface or in the cytoplasm of leukemia cells, B-ALL can be divided into 4 subtypes according to its stage of differentiation: pro-B, common B, pre-B, and immature B subtypes. This study aims to establish the association of the molecular biomarkers TCF3-PBX1 t(1;19), rearrangement of MLL t(4;11), BCR-ABL1 t(9;22), and ETV6-RUNX1 t(12;21) with ALL subtypes according to its stage of differentiation. The study includes a retrospective analysis of laboratory data results from the Mexican mestizo pediatric population diagnosed with ALL during a 3-year period (2018-2021), referred to Mendel laboratories from different health institutions. Ninety ALL cases, age range 0-17 years, were classified by immunophenotype and tested by PCR for the biomarkers TCF3-PBX1, rearrangement of MLL, BCR-ABL1, and ETV6-RUNX1. The biomarkers tested were expected to be present in most of the cases (>50%) regardless of the differentiated ALL subtype. B-cell ALL represented 92.2% of the cases (83); the prevailing subtype was pre-B with 51.1% of all cases. The biomarkers TCF3-PBX1, rearrangement of MLL, BCR-ABL1, and ETV6-RUNX1 were present in at least one case in the subtype pro-B. ETV6-RUNX1 was identified as the only marker in common B-ALL. Seventy-one percent of the cases showed no presence of the 4 biomarkers tested and correspond to quadruple negative cases. The biomarkers TCF3-PBX1, rearrangement of MLL, BCR-ABL1, and ETV6-RUNX1 are decisive in establishing the prognosis of patients with any of the ALL-B subtypes and enable the definition of a stratified treatment. The absence of these markers prevails in the study population, so it is essential to include other recently described mutations in laboratory determinations. Laboratorios MENDEL, Morelia Michoacán. México.

Mixed-Lineage Leukemia

Introduction: Acute Leukemia with Mixed Lineage phenotype (MLL) is leukemia that consists of cells characterized by mixed lineage markers, both from myeloid and lymphoid cells. The incidence of this leukemia is only 2-5% of all acute leukemias and is considered to have a poor prognosis.Case Presentation: A seven-year-old girl was diagnosed with MLL. The results of immunophenotyping showed two blast populations with the expressions of CD33, CD34, HLA-DR, CD117, CD13, CD19, CD10, CD20, CyMPO, Cy CD79a, and morphological features of Acute Lymphoblastic Leukemia (ALL) and Acute nonLymphocytic Leukemia (AnLL) on bone marrow aspiration. The BCR-ABL examination showed the detected BCR-ABL p210 (Major breakpoint), the majority of which was found in chronic myeloid leukemia (CML) patients. There is no definite pathogenesis of BCR-ABL p210 (MBCR-ABL) in this patient. BCR-ABL can also present in 11–29% of ALL patients but is relatively rare in childhood ALL (1%–3%) and mostly expresses p190 (minor breakpoint (mBCR-ABL)). The p210 BCR-ABL transcript is detected in 30% of adults and 20% of childhood ALL patients with Philadelphia ALL. Conclusions: MLL with BCR-ABL p210 transcript is very rare in acute leukemia. Immunophenotyping tests can detect typical MLL profiles, and WHO has standardized the diagnosis for MLL.

Health inequities in survival of patients with acute lymphoblastic leukemia in Peru: A single tertiary institution experience.

7012 Background: Acute Lymphoblastic Leukemia (ALL) in Latino countries is characterized by high incidence and worst outcomes compare to other ethnicities. However, the actual epidemiological characterization of ALL in South America remains unknown. The lack of registries, uniform treatment and prospective protocols have been pointed out for these disparities. Also, biological, and social aspects of this disease play an important role that has not been well examined. We aimed to evaluate the survival of patients with acute lymphoblastic leukemia according to demographic characteristics with emphasis in the place of residence. Methods: We performed an analytical retrospective cohort study with subjects diagnosed and treated for ALL during the period 2016-2018 at the Peruvian national cancer center (INEN, Instituto Nacional de Enfermedades Neoplasicas). INEN is currently the main center dedicated to diagnosing and treat acute leukemias for patients without social neither private insurance. Also, INEN is located at the capital city (Lima-Peru). The calculated sample size was 378 patients. Patient data were obtained from the epidemiological registry and corroborated with the national registry of mortality (RENIEC, Registro Nacional de Identificacion y Estado Civil Overall survival probabilities according to demographic characteristics were estimated using the Kaplan-Meier curve; in addition, the Log-rank test and Cox regression were used. Results: A sample of 378 patients were included during the study period (N = 588), of which 212 (56.8%) were male, 42% were between 0-10 years, 24% in 46-65 years. Regarding the characteristics at diagnosis, 80% were Ph(-) BCP-ALL and 69% corresponded to high-risk groups. At 42 months of follow-up, the median survival of the patients was 29 months (95% CI: 23.3-34.6), and the overall survival at three years was 44.8%. Overall survival in males (48.8%) was higher than in females (39.5%). According to the range of age, the highest survival was in the group of 0-10 years (70%), followed by 11-20 years (36.8%) and the lowest survival was in 46- 65 years (12.5%). Furthermore, overall survival in Lima (51.5%) was higher than in the country-side (39.7%). There was a statistically significant association (p &lt; 0.05) between survival and sex (p = 0.042), age range (p = 0.000) and place of residence (p = 0.005); according to the Log-rank test. Conclusions: We report a lower survival among all age groups in ALL compared to international working groups. Living in a country-side region represents a significant factor for dismal survival in our cohort. Specialized health care access to diagnosis and treatment should be warranted for patients with geographical limitations and programs to ensure it must be implemented.

Molecular and MRD-Based Characterization of Acute Lymphoblastic Leukemia in Mexico: Experience from the Mexico in Alliance with St. Jude “Bridge Project”

▪Background: Cancer is the second leading cause of death in Mexico among children 5-14 years. In 2017, Mexico in Alliance with St. Jude (MAS), a multi-site intersectoral collaboration, explored reasons for suboptimal outcomes for children with acute lymphoblastic leukemia (ALL). Results showed 82% of patients to be classified as high-risk and 30% of patients be missing standard molecular or minimal residual disease (MRD) studies needed to inform risk- group stratification. Making sense of the molecular characteristics was challenging in the context of variable access and lack of common denominators. These findings led to the development of the “Bridge Project”; a prospective quality improvement demonstration project aiming to bridge this access and quality gap through multi-site collaboration, centralization, and standardization.Methods: Six MAS collaborating hospitals, located in six different states (Mérida, Guadalajara, Sinaloa, Baja California, Chiapas, and Veracruz), have sent diagnostic samples for children 0-18 years old with suspected ALL to Hospital Infantil Teletón de Oncología (HITO), in Queretaro, which serves as the centralized laboratory for the MAS cooperative group. Access to the diagnostic panel is secured upfront through dedicated funding obtained from a local foundation. The first sample was shipped in July 2019. The consensus-derived diagnostic panel includes morphology, immunophenotype, karyotype, fluorescent in situ hybridization (FISH), molecular biology (RT-PCR) and flow cytometry (FC) MRD at two time points. Protocols vary by institution and MRD evaluation is only done if the institutional protocol incorporates MRD-evaluation into the risk-group stratification. Hospitals send several empty boxes prior to shipping patient samples to assess their regional shipping vendors and timelines. The also standardize data collection processes and use PDSA cycles to monitor sample quality and address issues with sample quality. HITO produces FC results (for diagnosis or MRD evaluation) and FISH/cytogenetic results within 3 to 21 days of sample arrival.Results: As of July 2021, the centralized lab has received samples from 217 patients with suspected ALL through this project and 93% of these samples have arrived within the 48hr target. Of these, 176 (81.1%) had confirmed ALL and 14 (6.4%) had acute myeloid leukemia (AML), 2 (0.9%) cases had other malignant conditions, and in 25 (11.5%) of the cases leukemia was ruled out. Among the 176 cases of confirmed ALL, 162 (92%) had B-cell lineage and 14 (8%) had T-cell lineage. FISH was reported for 172 (97.7%) patients and positive in 126 (73.2%) cases; 46 (26.7%) cases had reported gains, 34 (19.7%) detected t(12;21), 18 (10.4%) detected iAMP cr21, 8 (4.7%) detected breaks of the MLL gene t(4;11), 7 (4%) detected t(1;19), and 6 (3.4%) detected t(9;22). Four T-cell ALL cases had breaks CDKN2A del(9)(p21) and three cases had TRA/D rearrangement (14) (q11.2). Karyotype alterations were detected in 90 (52.3%) of the samples, of which 41 (23.8%) showed hyperdiploidy and 13 (7%) showed complex karyotype. One case of hypodiploid was identified. Day 15 MRD was assessed in 131 (80%) patients with B-cell lineage, Day 84 MRD was assessed in 99 (61.1%) patients with B-cell lineage, and Day 29 MRD in 8 (57.1%) patients with T-cell lineage whose treatment schema utilizes MRD-based stratification. Among B-lineage patients, 84% had MRD <1% at Day 15 and 94.9% MRD <0.01% at Day 84. Among T-cell lineage patients, 75% had MRD <0.01% at Day 29 and 80% MRD <0.01% at Day 84, but numbers for T-cell lineage were small.Conclusions: Given proper structural and financial supports, patients with suspected childhood ALL in Mexico can access a comprehensive diagnostic panel following a centralized laboratory approach. Preliminary results from the Bridge Project allow characterizing childhood ALL to a degree that has not been previously possible in Mexico. In this cohort, favorable characteristics such a t(12;21), gains, and hyperdiploidy are observed in frequencies similar to those reported in Hispanic cohorts in high-income countries. MRD results are for B-cell lineage are also consistent with the literature. Continued engagement in this project from hospitals in diverse geographic settings and with diverse patient populations will allow the MAS cooperative group to continue to improve the characterization of childhood ALL in Mexico. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Enolase 2-Mediated Glucose Metabolism Promotes Cell Proliferation and Survival in Acute Lymphoblastic Leukemia

Background: The metabolic profiles of cancer cells have long been acknowledged to be altered and to provide new therapeutic opportunities. Expression of glycolytic enzyme enolase 2(ENO2) was found to be closely related with clinical features of acute lymphoblastic leukemia (ALL) patients, but its functions are still unclear in ALL.Methods: We evaluated the association between ENO2 mRNA expression of bone marrow mononuclear cells(BM-MCs) and efficacy of chemotherapy, and further explored the function of ENO2 in ALL.Results: The results showed that ENO2 mRNA expression in BM-MCs was significantly decreased when patients completed induction chemotherapy and reached complete remission(CR). ENO2 mRNA expression was increased when patients suffered relapse. Functional study demonstrated that ENO2 promoted cell growth, glycolysis, and glucocorticoid-resistance, all of which were effectively inhibited when ENO2 was silenced with shRNAs. Further study found that ENO2 upregulated various glycolysis-related genes, and ENO2 enhanced Akt activity with subsequent Glycogen synthase kinase3β(GSK-3β) phosphorylation, inducing cell proliferation and glycolysis. The combination of silencing ENO2 and 2-deoxyglucose (2-DG) synergistically inhibited leukemia cell survival.Conclusion: These results indicate that ENO2 may be a biological marker for monitoring chemotherapeutic efficacy and relapse in ALL. ENO2 may provide a potential therapeutic strategy for ALL. DisclosuresNo relevant conflicts of interest to declare.

Acute lymphoblastic leukemia (ALL) is one of the most common malignancies of childhood. Peripheral blood and bone marrow involvement is common. Extramedullary involvement of central nervous system, liver, spleen, skin and testicles are seen. ALL presenting as nephromegaly is exceedingly rare. This case is reported for its rare presentation as nephromegaly. Bone marrow aspirate showed features of acute lymphoblastic leukemia

Acute lymphoblastic leukemia ALL is one of the most common malignancies of childhood. Peripheral blood and bone marrow involvement is common. Extramedullary involvement of central nervous system liver spleen skin and testicles are seen. ALL presenting as nephromegaly is exceedingly rare. This case is reported for its rare presentation as nephromegaly. Bone marrow aspirate showed features of acute lymphoblastic leukemia and immunophenotyping by flow cytometry confirmed the diagnosis.

Immunophenotypic characterization of acute lymphoblastic leukemia in a flowcytometry reference centre in Sri Lanka.

Acute lymphoblastic leukemia (ALL), is a biologically heterogeneous disease where diagnosis, treatment and prognosis is heavily dependent on the correct characterization of the immunophenotype of each case. To describe the immunophenotypic and laboratory features of a cohort of Sri Lankan children and adults with ALL and to compare them with those reported in other series. Records of 229 patients who were suspected of having acute leukaemia and referred for flow cytometry to the Asiri Hospital Sri Lanka, between August 2009 and October 2013 were reviewed. Referrals were from across the country including the National Cancer Institute. Sixty seven percent were children below 12 years of age. 80% had B-lymphoblastic leukaemia (B-ALL), 20% T- lymphoblastic leukaemia (T-ALL). In children, the peak age of diagnosis was between 2-6 years in B-ALL (61%) and 3-6 years (43.7%) in T-ALL. Incidence was commoner in males in all age groups and subtypes except in the adult B ALL group where the incidence was equal. Ninety three percent of paediatric B-ALL and 67% adult B-ALL were CD10 positive common ALL. In T-ALL cytoplasmic expression of CD3 was 100%. nTdT was the most commonly expressed immature marker, in B-ALL - 91% and in T-ALL- 69%. At least one myeloid antigen was present in 34% of B-ALL cases and 60% of T-ALL cases. This study represents the first immunophenotype based description of ALL in Sri Lanka. Age, sex distribution, ALL subtypes and the immunophenotypic profile of each subtype mirrored those of previous studies.

&lt;em&gt;ADAM3A&lt;/em&gt; deletion is associated with high‑risk features in acute lymphoblastic leukemia

&lt;em&gt;ADAM3A&lt;/em&gt; deletion is associated with high‑risk features in acute lymphoblastic leukemia

No association between BCR-ABL1 fusion genes and clinical features of acute lymphoblastic leukaemia in Ghanaian patients

INTRODUCTION: The BCR-ABL1 fusion gene has been associated with poor prognosis in acute lymphoblastic leukaemia (ALL). This study was designed to determine the presence, frequency and associated laboratory and clinical features of the BCR-ABL1 gene in Ghanaian patients diagnosed with ALL. METHODS: this was a cross-sectional study using archival methanol-fixed bone marrow aspirate slides of morphologically diagnosed ALL patients. Presence of the BCR-ABL1fusion gene was determined by fluorescent in situ hybridization. Clinical features and haematological parameters were extracted from the patients´ medical records. RESULTS: seventeen patients were studied, 13 (76.5%) males and 4 (23.5%) females. Median age was 24 years (range 15 to 67 years). A frequency of 29.4% was obtained for the BCR-ABL1 fusion gene. There was no significant association between presence of BCR-ABL1 and selected clinical features (lymphadenopathy, splenomegaly and hepatomegaly). All patients had moderate to severe anaemia with median haemoglobin concentration of 7.6 g/dL (range 3.7 to 8.7 g/dL). Median haemoglobin concentration for BCR-ABL1 positive patients was higher than that for negative patients (7.6 vs. 7.4 g/dL, p = 0.506); who also had higher median white blood cell counts (24.76 vs. 13.02 X 109/L), but lower median platelet counts (58.0 vs. 64.5 X 109/L, p = 0.721) and bone marrow blast percentages (78.5 vs. 98.0 %, p = 0.851) compared to negative patients. Conclusion: BCR-ABL1 fusion gene was detected in nearly one third of adult ALL patients in this study, with no significant association with common haematological parameters and clinical features of the disease.

Investigation of NF-κB-94ins/del ATTG and CARD8 (rs2043211) Gene Polymorphism in Acute Lymphoblastic Leukemia

NLRP3 inflammasome has been widely implicated in the development and progression of various hematological diseases. However, how NLRP3 inflammasome contributes to the pathogenesis and clinical features of acute lymphoblastic leukemia (ALL) is still unknown. Here, in ALL patients' bone marrow, we investigated the single-nucleotide polymorphisms (SNPs) and expression of NLRP3 inflammasome related genes, NF-κB, NLRP3, IL-1β, IL-18, Caspase-1, and ASC. A total of 308 ALL patients and 300 healthy participants were included in this study. D allele and DD genotype under codominant model of NF-κB-94ins/del ATTG were showed as a protective factor in susceptibility of ALL. As for CARD8 (rs2043211), AT/TT genotype under dominant model and TT genotype under codominant model greatly increased the ALL susceptibility. We further studied the relationship between NLRP3 inflammasome genetic polymorphisms and clinical relevance. The results showed that DD genotype of NF-κB-94 ins/del ATTG and AT/TT genotype of CARD8 (rs2043211) contributed to lower WBC count and T-cell immunophenotype, respectively. Moreover, we also found that AT and TT genotypes of CARD8 (rs2043211), GT and TT genotypes of IL-1β (rs16944), and TT genotype of IL-18 (rs1946518) were associated with higher mRNA expression of NLRP3 inflammasome related genes and secretion of downstream cytokines. In conclusion, NF-κB-94 ins/del ATTG and CARD8 (rs2043211) genotypes might serve as novel biomarkers and potential targets for ALL.

Impact of cytogenetics on outcomes in pediatric acute lymphoblastic leukemia.

Context:In acute lymphoblastic leukemia (ALL), the most important prognostic factors are age, leukocyte count at presentation, immunophenotype, and cytogenetic abnormalities. The cytogenetic abnormalities are associated with distinct immunologic phenotypes of ALL and characteristic outcomes.Aims:The present study was primarily aimed at analyzing the impact of cytogenetics on postinduction responses and event-free survival (EFS) in pediatric patients with ALL. The secondary objective was to study the overall survival (OS).Subjects and Methods:A total of 240 patients with age <18 years and diagnosed with ALL between January 2011 and June 2016 were retrospectively analyzed. Cytogenetics was evaluated with conventional karyotyping or reverse transcriptase polymerase chain reaction. Based on cytogenetic abnormalities, the patients were grouped into five categories, and the outcomes were analyzed.Results:Of the 240 patients, 125 (52%) patients had evaluable cytogenetics. Of these, 77 (61.6%) patients had normal cytogenetics, 19 (15.2%) had t(9;22) translocation, 10 (8%) had unfavorable cytogenetics which included t(9;11), hypodiploidy, and complex karyotype, 10 (8%) had favorable cytogenetics which included t(12;21), t(1;19), and high hyperdiploidy, 9 (7.2%) had miscellaneous cytogenetics. Seventy-one percent of patients were treated with MCP 841 protocol, while 29% of patients received BFM-ALL 95 protocol. The 3-year EFS and OS of the entire group were 52% and 58%, respectively. On univariate analysis, EFS and OS were significantly lower in t(9;22) compared to normal cytogenetics (P = 0.033 and P = 0.0253, respectively) and were not significant for other subgroups compared to normal cytogenetics. On multivariate analysis, EFS was significantly lower for t(9;22) and unfavorable subgroups.Conclusions:Cytogenetics plays an important role in the molecular characterization of ALL defining the prognostic subgroups. Patients with unfavorable cytogenetics and with t(9;22) have poorer outcomes.

ENO2 Promotes Cell Proliferation, Glycolysis, and Glucocorticoid-Resistance in Acute Lymphoblastic Leukemia

Background/Aims: The metabolic features of cancer cells have long been acknowledged to be altered and to provide new therapeutic opportunities. The expression of glycolytic enzyme enolase 2 (ENO2) was found to be closely associated with the clinical features of acute lymphoblastic leukemia (ALL) patients, but its functions remain unclear in ALL. Methods: We evaluated the association between ENO2 mRNA expression in bone marrow mononuclear cells (BM-MNCs) and the efficacy of chemotherapy, and further explored the function of ENO2 in ALL. The molecular mechanisms of ENO2 expression and its effects on cell growth, glycolysis and glucocorticoid resistance were explored by Cell Counting Kit-8, glucose-consumption assay, Quantitative RT-PCR, Western blotting and in vivo tumorigenesis in NOD/SCID mice. Results: The results showed that ENO2 mRNA expression in BM-MNCs was significantly decreased when patients completed induction chemotherapy and reached complete remission (CR). ENO2 mRNA expression was increased when patients suffered relapse. Functional studies demonstrated that ENO2 promoted cell growth, glycolysis, and glucocorticoid resistance, all of which were effectively inhibited when ENO2 was silenced with shRNAs. Further studies revealed that ENO2 up-regulated various glycolysis-related genes and enhanced Akt activity with subsequent glycogen synthase kinase3β (GSK-3β) phosphorylation, inducing cell proliferation and glycolysis. The combination of silencing ENO2 and 2-deoxyglucose (2-DG) synergistically inhibited leukemia cell survival. Conclusions: These results indicate that ENO2 may be a biological marker for monitoring chemotherapeutic efficacy and relapse in ALL. ENO2 may provide a potential therapeutic strategy for ALL.

Immunophenotypic Profile in Adult Patients with Acute Leukemia Association with Clinical Feature: Fluorescence Cytometry Quantitative Analysis

Antigen surface markers represent as the new prognostic tool for detection of acute leukemia. To investigate the prevalence expression of lymphoid and myeloid antigen lineage in acute leukemias. This study included 100 acute leukemias patients. Specimens were selected from consecutive patients who had sufficient material available. Among the 100 patients in which a detailed history, hematological, clinical and immunophenotyping analysis were performed. This study was showed distribution of immunophenotyping characters between studied AML and ALL cases. The most abundant immunophenotyping features in acute myeloid leukemia were cMPO, CD33, CD117, CD13, CD14 and CD64, while the most abundant immunophenotyping features in acute lymphoblastic leukemia were CD19, CD79a, TdT, CD20, CD10 and CD34. cMPO which act as independent prognostic factor for AML, CD10 and TdT can used as independent prognostic factor for differentiate between ALL and AML.

Vertebral Compression Fractures as a Presenting Feature of AcuteLymphoblastic Leukemia

Acute lymphoblastic leukemia is one of the most common malignancies in children and adolescent accounting for 30% of all the cancers. We report an interesting case of Acute lymphoblastic leukaemia(ALL) with an unusual presentation.This 15–year- old girl came with a progressive low back pain for three months following a history of fall for 5 month ago with intact consciousness. The physical examination showed gibbus over lumbar spine with tenderness. Images showed generalized osteopenia with multiple vertebral body collapse.Complete blood count revealed pancytopenia with raised ESRwithout any blast cell. Bone marrow aspirate was suggestive of ALL.Young ALL patients usually present with symptoms due to cytopenias, fever and bone pains. Although asymptomatic skeletal involvement may be present in patients with ALL, rarely patients present with pathological fractures. Therefore a high index of suspicion is needed to diagnose such case.J MEDICINE July 2016; 17 (2) : 120-121

Evaluation of cost effective diagnostic tools in characterisation of Acute Leukemia in Southern India.

The incidence of Acute Leukemia (AL) subtypes varies according to geographical distribution and more predominant in developing countries. The aim here was to evaluate the usefulness of cost effective diagnostic tools in characterization of Acute Lymphoblastic Leukemia (ALL) in resource poor population. One hundred and two AL cases were diagnosed. For diagnosis, cytochemical analysis and immunohistochemistry were performed. Among the children < 12 years, ALL was 64.3% while AML accounted for 30%. In patients > 12 years, ALL was 59.4% and AML was 31.3%. The B-ALL occurred most frequently than T-ALL in both the age groups while based on immunophenotyping in AML, CD13 was the most commonly expressed antigen. Hence, cost effective diagnostic tools namely the immunophenotyping and cytochemistry are useful and improve accuracy and rapidly risk-stratify patients that were diagnosed with acute leukemia.

Serum neuron-specific enolase levels are upregulated in patients with acute lymphoblastic leukemia and are predictive of prognosis.

We explored the relationship between neuron-specific enolase (NSE) levels and the clinical features of acute lymphoblastic leukemia (ALL). Seventy ALL patients and forty-two healthy controls were enrolled in this study, and their serum NSE levels were measured using an electrochemiluminescence assay. The serum NSE concentration was higher in ALL patients than in healthy controls. In ALL patients, the mean serum NSE level declined after complete remission (CR) but increased with relapse. In addition, the mean serum NSE level was lower in the CR group than in the non-CR group. High NSE levels were associated with poorer progression-free and overall survival than low NSE levels. Serum NSE levels closely correlated with several clinical features, including the immunophenotype, risk stratification and serum lactate dehydrogenase levels. Multivariate analysis revealed that high NSE expression was an independent prognostic factor in adult ALL patients. NSE mRNA levels were also higher in ALL cell lines and bone marrow mononuclear cells from ALL patients than in control cells. These results suggested that NSE could be a clinical prognostic factor and a potential therapeutic target in ALL.

Frequency and clinical impact of ETV6/RUNX1, AF4-MLL, and BCR/ABL fusion genes on features of acute lymphoblastic leukemia at presentation.

Variations in disease presentation and outcome of leukemia treatment has been associated with the presence of certain mutant genes. Three major translocations (ETV6-RUNX1, BCR-ABL, and AF4-MLL) in acute lymphoblastic leukemia (ALL) have been shown to affect treatment outcome. This study is aimed at assessing the relationship between these translocations and the presence of other indicators of disease severity (white cell count, hemoglobin concentration, platelet count, and hematocrit) in ALL. Forty chemotherapy naïve patients aged between 9 months and 54 years had their marrow samples analyzed for the prevalent mutations. Their clinical and laboratory details on presentation were also obtained. Abnormal genes detected were BCR/ABL1 major transcript in 5 (12.5%), ETV6/RUNX1 in 2 (5.0%), MLL/AF4 none and none of the patients had more than one fusion gene. There was no relationship between the presence of these fusion genes and the clinical and laboratory features of ALL. An association exists between the fusion genes and ethnic origin of the patients (P = 0.005). There is no significant association between the abnormal fusion genes detected and some laboratory features of prognostic importance, which include total white blood cell count (P = 0.416) and FAB subtype (P = 0.576). Presence of fusion the genes BCR/ABL1, ETV6/RUNX1, and MLL/AF4 does not have any impact on the clinical and laboratory features of ALL at presentation.