Childhood Acute Lymphoblastic Leukemia Research Articles

Effect of XRCC1 Arg399Gln Gene Polymorphism on Survival in Lymphoblastic Leukemia.

The relevance of the research of the article is conditioned upon the problem of the development of molecular genetic diagnostics to determine the effectiveness of treatment for acute lymphoblastic leukemia in children. The purpose of the article is to identify the polymorphism parameters of the P53 Arg72Pro and XRCC1 Arg399Gln genes in acute lymphoblastic leukemia with criteria for determining the survival rates of sick children. Methods for the study of the identified problem are the study of the medical histories of children with acute leukemia, which allowed selection of the necessary contingent of patients for further genetic study of their frozen blood, where the genomic part of deoxyribonucleic acid was isolated from the frozen blood in a standard way using molecular biological research when performing a polymerase chain reaction. The article presents the results of a study that shows that in children with acute lymphoblastic leukemia, the frequency of genotypes of the XRCC1 Arg399Gln gene is variable. The most common genotypes are Arg/Gln and Arg/Arg, approximately 48% each. The Gln/Gln genotype is less common. Relapse-free survival of children with the Arg/Gln and Gln/Gln genotypes was the highest, slightly lower rates were noted with the Arg/Arg genotype. It was identified that the frequency of genotypes of the XRCC1 Arg399Gln gene can be a predictor of prognosis in acute lymphocytic leukemia in children, which can be considered when choosing treatment tactics, and this has practical significance for the field of medicine.

The Prognostic Effect of IKZF1 Deletions in ETV6::RUNX1 and High Hyperdiploid Childhood Acute Lymphoblastic Leukemia.

IKZF1 deletions are an established prognostic factor in childhood acute lymphoblastic leukemia (ALL). However, their relevance in patients with good risk genetics, namely ETV6::RUNX1 and high hyperdiploid (HeH), ALL remains unclear. We assessed the prognostic impact of IKZF1 deletions in 939 ETV6::RUNX1 and 968 HeH ALL patients by evaluating data from 16 trials from 9 study groups. Only 3% of ETV6::RUNX1 cases (n = 26) were IKZF1-deleted; this adversely affected survival combining all trials (5-year event-free survival [EFS], 79% versus 92%; P = 0.02). No relapses occurred among the 14 patients with an IKZF1 deletion treated on a minimal residual disease (MRD)-guided protocols. Nine percent of HeH cases (n = 85) had an IKZF1 deletion; this adversely affected survival in all trials (5-year EFS, 76% versus 89%; P = 0.006) and in MRD-guided protocols (73% versus 88%; P = 0.004). HeH cases with an IKZF1 deletion had significantly higher end of induction MRD values (P = 0.03). Multivariate Cox regression showed that IKZF1 deletions negatively affected survival independent of sex, age, and white blood cell count at diagnosis in HeH ALL (hazard ratio of relapse rate [95% confidence interval]: 2.48 [1.32-4.66]). There was no evidence to suggest that IKZF1 deletions affected outcome in the small number of ETV6::RUNX1 cases in MRD-guided protocols but that they are related to higher MRD values, higher relapse, and lower survival rates in HeH ALL. Future trials are needed to study whether stratifying by MRD is adequate for HeH patients or additional risk stratification is necessary.

The influence of RANKL/osteoprotegerin on the prognosis of childhood acute lymphoblastic leukemia

Aims: The aim is to investigate the association of the osteoprotegerin (OPG)/ soluble(s) receptor activator nuclear kappa B ligand (RANKL) with the prognosis of children with acute lymphoblastic leukemia (ALL). Methods: Patients with the diagnosis of ALL between the years 2008-2010, were enrolled in the study. Demographic characteristics and complete blood count findings, treatment responses, as well as OPG and sRANKL levels were evaluated on admission and at the end of induction treatment. Results: Mean serum levels of OPG and sRANKL on admission were 38,6 ±19,03 ng/ml and 0,22±0,24 ng/ml, respectively. Whereas, at the end of induction, serum levels were measured as 35,5±40,8 ng/ml for OPG and 0,033±0,056 ng/ml for sRANKL. A statistically significant decrease was determined for sRANKL at the end of induction therapy, compared to admission (p:0,000). Conclusion: In the current research, OPG and sRANKL are increased at diagnosis of childhood B-ALL. Whereas, no significant relationship between the OPG and sRANKL levels and the disease prognosis was determined.

The Clinicogenomic Landscape of Induction Failure in Childhood and Young Adult T-Cell Acute Lymphoblastic Leukemia.

Failure to respond to induction chemotherapy portends a poor outcome in childhood acute lymphoblastic leukemia (ALL) and is more frequent in T-cell ALL (T-ALL) than B-cell ALL. We aimed to address the limited understanding of clinical and genetic factors that influence outcome in a cohort of patients with T-ALL induction failure (IF). We studied all cases of T-ALL IF on two consecutive multinational randomized trials, UKALL2003 and UKALL2011, to define risk factors, treatment, and outcomes. We performed multiomic profiling to characterize the genomic landscape. IF occurred in 10.3% of cases and was significantly associated with increasing age, occurring in 20% of patients age 16 years and older. Five-year overall survival (OS) rates were 52.1% in IF and 90.2% in responsive patients (P < .001). Despite increased use of nelarabine-based chemotherapy consolidated by hematopoietic stem-cell transplant in UKALL2011, there was no improvement in outcome. Persistent end-of-consolidation molecular residual disease resulted in a significantly worse outcome (5-year OS, 14.3% v 68.5%; HR, 4.10; 95% CI, 1.35 to 12.45; P = .0071). Genomic profiling revealed a heterogeneous picture with 25 different initiating lesions converging on 10 subtype-defining genes. There was a remarkable abundance of TAL1 noncoding lesions, associated with a dismal outcome (5-year OS, 12.5%). Combining TAL1 lesions with mutations in the MYC and RAS pathways produces a genetic stratifier that identifies patients highly likely to fail conventional therapy (5-year OS, 23.1% v 86.4%; HR, 6.84; 95% CI, 2.78 to 16.78; P < .0001) and who should therefore be considered for experimental agents. The outcome of IF in T-ALL remains poor with current therapy. The lack of a unifying genetic driver suggests alternative approaches, particularly using immunotherapy, are urgently needed.

Expression pattern of miR-16-2-3p and its prognostic values on pediatric acute lymphoblastic leukemia

Acute lymphoblastic leukemia (ALL) is a debilitating illness that easily occurs in adolescents. microRNAs (miRNAs) are potential biomarkers for multiple diseases. This paper was to elaborate on the expression of miR-16-2-3p in childhood ALL and its clinical values on ALL diagnosis and prognosis. First, serum miR-16-2-3p expression in ALL children and healthy volunteers was measured using RT-qPCR. Next, diagnostic potential and prognostic values of miR-16-2-3p on ALL were analyzed through receiver operating characteristic (ROC) curve, Kaplan–Meier survival curve, and multivariate Cox regression analysis, respectively. No significant difference was observed in the clinical baseline data between ALL patients and healthy children. ALL patients showed downregulated serum miR-16-2-3p (0.65 ± 0.27) (p < .01), whose area under the ROC curve was 0.837 with a cut-off value of 0.745 (67.92% sensitivity, 96.94% specificity). ALL patients with higher miR-16-2-3p expression had higher survival rates than those with lower miR-16-2-3p expression. Low miR-16-2-3p expression predicted poor prognosis of ALL patients. After adjusting LDH and lymphomyelocyte proportion (p = 0.003, HR = 0.003, 95%CI = 0.000–0.145), miR-16-2-3p was recognized as an independent prognostic factor for ALL patient survival. Briefly, low serum miR-16-2-3p expression in ALL children could aid ALL diagnosis and predict poor prognosis.

Vincristine induced peripheral neuropathy in children undergoing chemotherapy for acute lymphoblastic leukaemia during induction

Background: Vincristine is an anticancer agent administered to all children with acute lymphoblastic leukemia (ALL), and peripheral neuropathy is the major dose-limiting toxicity of this therapy. As cure rates of childhood ALL exceeds 80%, therefore treatment-related toxicities need to be reduced. Thus, the aim of this study was to determine the prevalence and risk factors of vincristine-induced peripheral neuropathy (VIPN) in children with ALL undergoing induction chemotherapy. Methods: A case-control study was conducted from September 2017 to August 2018 in the Department of Paediatric Haematology and Oncology at Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh. Eighty newly diagnosed ALL and 35 acute myeloid leukemia (AML) cases aged 5 to 17 years with no pre-existing neurological abnormality were recruited. To assess the peripheral neuropathy, we used pediatric-modified total neuropathy score and National Cancer Institute- Common Terminology Criteria for Adverse Events (NCI-CTCAE), version-04 grade. Results: Among ALL patients, 29.2% developed peripheral neuropathy compared to 10% in AML control group (P=0.04). Higher proportion (57.1%) of peripheral neuropathy was found in age below 10 years (P&lt;0.001). There was no significant association of peripheral neuropathy with sex and body mass index of the patients. Conclusion: Almost 3 in 10 patients developed VIPN during the induction therapy which is significantly higher in age below 10 years compared to ≥ 10 years.

Optimized treatment of childhood B-lineage acute lymphoblastic leukemia

Childhood acute lymphoblastic leukemia (ALL) accounts for about 75% of childhood leukemia cases, and B-lineage acute lymphoblastic leukemia (B-ALL) accounts for more than 80% of childhood ALL cases. Over the past half century, new molecular biological targets discovered by new techniques have been used in precise stratification of disease prognosis, and there has been a gradual increase in the 5-year overall survival rate of childhood ALL. With the increasing attention to long-term quality of life, the treatment of childhood B-ALL has been constantly optimized from induction therapy to the intensity of maintenance therapy, including the treatment of extramedullary leukemia without radiotherapy, which has been tried with successful results. The realization of optimized treatment also benefits from the development of new techniques associated with immunology and molecular biology and the establishment of standardized clinical cohorts and corresponding biobanks. This article summarizes the relevant research on the implementation of precise stratification and the intensity reduction and optimization treatment of B-ALL in recent years, providing reference for clinicians.

L-Asparaginase as the gold standard in the treatment of acute lymphoblastic leukemia: a comprehensive review.

L-Asparaginase is an antileukemic drug long approved for clinical use to treat childhood acute lymphoblastic leukemia, the most common cancer in this population worldwide. However, the efficacy and its use as a drug have been subject to debate due to the variety of adverse effects that patients treated with it present, as well as the prompt elimination in plasma, the need for multiple administrations, and high rates of allergic reactions. For this reason, the search for new, less immunogenic variants has long been the subject of study. This review presents the main aspects of the L-asparaginase enzyme from a structural, pharmacological, and clinical point of view, from the perspective of its use in chemotherapy protocols in conjunction with other drugs in the different treatment phases.

Impact of TP53 gene variants on prognosis and survival of childhood acute lymphoblastic leukemia

The tumor suppressor protein 53 (TP53) gene is one of the most studied genes in cancer. Although TP53 variants are rare events in acute leukemia, recent observations showed that relapse samples might harbor TP53 variants. Here, we aimed to determine TP53 variants (hotspot region, exon 4–11) in childhood acute lymphoblastic leukemia (B and T-ALL) patients (n = 94) including diagnostic-relapse pairs (n = 15) by amplicon sequencing and evaluate the clinical impact of these variants. In total, nine different (E298*, R283C, R273H, L252F, C229F, I195T, E286G, c.955_956insC, and c.920-1G > C) variants were identified in 17 (18%) childhood ALL patients. c.(920-1G> C) splice site variant and c.(955_956insC) insertion were reported for the first time. In diagnose-relapse pair samples, we identified acquired and/or loss of TP53 variants in the samples at the time of relapse. TP53 variants were found to be more common in T-ALL (37%) than in B-ALL patients (9%). Pathogenic TP53 variants were associated with a shorter overall survival time (p = 0.001).TP53 variants were found to be associated with inferior outcomes in our cohort and can be an independent risk factor for poor prognosis in childhood acute leukemia patients. Identification of low-frequent variants with next-generation sequencing approaches enables better knowledge of the clonal dynamics of ALL.

Effect of two additional doses of intrathecal methotrexate during induction therapy on serious infectious toxicity in pediatric patients with acute lymphoblastic leukemia.

Although initial central nervous system (CNS) involvement is rarely detected in childhood acute lymphoblastic leukemia (ALL), risk-adapted CNS-directed therapy is essential for all patients. Treatment intensity depends on the initial CNS status. In the AIEOP-BFM ALL 2009 trial, patients with cytomorphologic detection of leukemic blasts in initial cerebrospinal fluid were classified as CNS2 or CNS3 and received five intrathecal doses of methotrexate (MTX) in induction therapy compared to patients with CNS1 status (no blasts detected) who received three doses. The impact of additional intrathecal (IT) MTX on systemic toxicity in induction therapy is unknown. Between June 1st 2010 and February 28th 2017, a total of 6,136 ALL patients aged 1-17 years were enrolled onto the AIEOP-BFM ALL 2009 trial. The effect of three versus five doses of IT MTX during induction therapy on the incidence of severe infectious complications was analyzed. Among 4,706 patients treated with three IT MTX doses, 77 (1.6%) had a life-threatening infection during induction as compared to 59 of 1,350 (4.4%) patients treated with five doses (P<0.001; Odds Ratio 2.86 [95% Confidence Interval 1.99-4.13]). In a multivariate regression model, treatment with additional IT MTX proved to be the strongest risk factor for life-threatening infections (Odds Ratio 2.85 [1.96-4.14]). Fatal infections occurred in 16 (0.3%) and 38 (1.6%) patients treated with three or five IT MTX doses, respectively (P<0.001). As the relevance of additional intrathecal MTX in induction for relapse prevention in CNS2 patients is unclear, doses of intrathecal therapy have been reduced for these patients. (Clinicaltrials.gov identifiers: NCT01117441 and NCT00613457).

Maternal and Paternal Household Pesticide Exposure During Pregnancy and Risk of Childhood Acute Lymphoblastic Leukemia.

The aim of this study was to investigate whether risk estimates for childhood acute lymphoblastic leukemia change when restricting model comparison groups to "nonpesticide exposure" (NPE10) households. Cases ( n = 1810) 15 years or younger were identified through Children's Cancer Group institutions between 1989 and 1993 and age-/sex-matched to controls ( n = 1951). Household pesticide use during pregnancy/month prior was collected via telephone. NPE10 comparison group reporting no parental exposure to 10 pesticide classes was identified. Adjusted odds ratios increased from 15% to 49% when limiting the comparison to NPE10. Maternal termite insecticide exposure was associated with greatest risk (adjusted odds ratio, 4.21; 95% confidence interval, 2.00-8.88). There was minimal evidence of interaction by child sex or occupational pesticide exposure, and no monotonic dose-response pattern with frequency of use (times per year). Elevated risks are consistent with published pooled-/meta-analyses and DNA damage. The consistency and magnitude of these associations warrant product labeling, exposure reduction interventions, or both.

Abstract 5216: The effect of polymorphisms in DAT1 and DRD4 on dietary intake during chemotherapy for childhood leukemia

Abstract Outcomes of acute lymphoblastic leukemia (ALL) are associated with both host and environmental factors. We hypothesized that there is also an interaction between them, with genetic variants influencing dietary choices. The dopamine transporter 1 (DAT1) and D4 subtype of the dopamine receptor (DRD4) genes are polymorphic, with a variable number of nucleotide repeats (VNTR) that affect dopaminergic neurotransmission, and reward circuitry for food cravings. Specifically, the 9-tandem repeats (9R) allele of DAT1 and the 7-tandem repeats (7R) allele of DRD4 are risk factors for eating disorders or undereating behavior in children. The goal of this study was to determine whether these polymorphisms are associated with altered dietary intake during therapy for childhood ALL. DNA was isolated from peripheral blood mononuclear cells collected from 439 children being treated on Dana Farber Cancer Institute ALL Consortium Protocol 05-001 (NCT00400946). Target alleles in DAT1 and DRD4 were determined using PCR product length analysis. Each subject was classified as having either zero or at least one copy of the target alleles. Dietary intake was previously determined using food frequency questionnaires collected at three timepoints: time of diagnosis, end of induction, and continuation therapy. As previously published dietary composition in fat and carbohydrate differed significantly among three timepoints. There was no significant difference between those with or without the target alleles in DAT1 or DRD4 in percent from fat or percent from carbohydrate at any of the three timepoints. However, significant differences were observed when dietary intake was compared to the Dietary Reference Intake (DRI). Notably, a greater portion of male participants with DAT1 9R polymorphism had fat consumption below the DRI at the time of diagnosis. On the contrary, significantly decreased portion of females with DAT1 9R had fat consumption below the DRI during continuation therapy. When compared to normative values, a significantly increased number of children had total calorie consumption below DRI during induction therapy. The DRD4 7R polymorphism was associated with fat intake below DRI during induction therapy in males. However, neither DAT1 nor DRD4 polymorphisms were related to variation in carbohydrates consumption. In addition, a greater portion of participants that carry both DAT1 and DRD4 polymorphism exhibited a trend toward undereating behavior in fat intake compared to the controls. Our results are the first to indicate that DAT1 and DRD4 polymorphisms are associated with altered dietary intake during chemotherapy for childhood ALL. Future study will further elucidate whether this modulation is associated with changes in their body weight, BMI, glucose level, and disease relapse. Citation Format: Jing Wen, Arul Duggimpudi, Shengguo Li, Elena Ladas, Kara M. Kelly, Peter D. Cole. The effect of polymorphisms in DAT1 and DRD4 on dietary intake during chemotherapy for childhood leukemia. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 5216.

Thiopurine Methyltransferase Intermediate Metabolizer Status and Thiopurine-Associated Toxicity During Maintenance Therapy in Childhood Acute Lymphoblastic Leukemia.

Mercaptopurine is a cornerstone of maintenance chemotherapy in childhood acute lymphoblastic leukemia (ALL). Its cytotoxic effects are mediated by 6-thioguanine nucleotides (TGNs) incorporation into lymphocyte DNA. Thiopurine methyltransferase (TPMT) inactivates mercaptopurine, and deficiency resulting from genetic variants increases TGN exposure and hematopoietic toxicity. Although mercaptopurine-dose reduction reduces toxicity risk without compromising relapse rate in patients with TPMT deficiency, dosing recommendations for those with moderately reduced activity (intermediate metabolizer (IM)) are less clear and their clinical impacts have yet to be established. This cohort study assessed the effect of TPMT IM status on mercaptopurine-associated toxicity and TGN blood exposure in pediatric patients with ALL initiated on standard dose mercaptopurine. Of 88 patients studied (mean age 4.8 years), 10 (11.4%) were TPMT IM, and all had undergone ≥ 3 cycles of maintenance therapy (80% completed). A larger proportion of TPMT IM than normal metabolizers (NM) had febrile neutropenia (FN) during the first two cycles of maintenance, reaching significance in the second cycle (57% vs. 15%, respectively; odds ratio=7.33, P < 0.05). Compared to NM, FN events occurred more frequently and with prolonged duration in IM in cycles 1 and 2 (adjusted P < 0.05). IM had a 2.46-fold increased hazard ratio for FN, and about twofold higher TGN level than NM (P < 0.05). Myelotoxicity was more common in IM than NM (86% vs. 42%, respectively) during cycle 2 (odds ratio=8.2, P < 0.05). TPMT IM initiated at a standard mercaptopurine dose are at greater risk for FN during early cycles of maintenance therapy, thus our findings support genotype-guided dose adjustment to reduce toxicity.

Clinical Significance of SFRP1 Gene Methylation in Patients with Childhood Acute Lymphoblastic Leukemia

To investigate the clinical significance of SFRP1 gene and its methylation in childhood acute lymphoblastic leukemia (ALL) . Methylation-specific PCR (MSP) was used to detect the methylation status of SFRP1 gene in bone marrow mononuclear cells of 43 children with newly diagnosed ALL before chemotherapy (primary group) and when the bone marrow reached complete remission d 46 after induction of remission chemotherapy (remission group), the expression of SFRP1 mRNA was detected by quantitative real-time polymerase chain reaction (qRT-PCR), the expression of SFRP1 protein was detected by Western blot, and clinical data of children were collected, the clinical significance of SFRP1 gene methylation in children with ALL was analyze. The positive rate of SFRP1 gene promoter methylation in the primary group (44.19%) was significantly higher than that in the remission group (11.63%) (χ2=11.328, P<0.05). The relative expression levels of SFRP1 mRNA and protein in bone marrow mononuclear cells of children in the primary group were significantly lower than those in the remission group (P<0.05). Promoter methylation of SFRP1 gene was associated with risk level (χ2=15.613, P=0.000) and survival of children (χ2=6.561, P=0.010) in the primary group, children with SFRP1 hypermethylation had significantly increased risk and shortened event-free survival time, but no significant difference in other clinical data. Hypermethylation of SFRP1 gene promoter may be involved in the development of childhood ALL, and its hypermethylation may be associated with poor prognosis.

Çocukluk Çağı Akut Lenfoblastik Lösemi Hastalarında Tedavi Sırasında Gelişen Akut Endokrin ve Metabolik Komplikasyonların Retrospektif Değerlendirilmesi

Çocukluk Çağı Akut Lenfoblastik Lösemi Hastalarında Tedavi Sırasında Gelişen Akut Endokrin ve Metabolik Komplikasyonların Retrospektif Değerlendirilmesi

Expression of nuclear pore protein POM121 in childhood acute lymphoblastic leukemias and its relationship with prognosis

Purpose: We aimed to investigate the status of POM121 gene expression, which is one of the nuclear pore proteins in childhood acute lymphoblastic leukemias (ALL), compared with the normal population, and its relationship with prognosis and other clinical findings.&#x0D; Materials and Methods: Fifty-nine patients with ALL followed up and treated between January 2008 and November 2013, and 36 control subjects were included in the study. A real-time PCR method was used to detect POM121 gene expressions.&#x0D; Results: The mean value of POM121 expression was 3.75±2.91 in ALL patients and 3.32±3.76 in the control group. The 3 and 10 year overall survival (OS) was better in ALL with lower POM121 expression (77%, 70% versus 68%, 58%, respectively). Although the OS was better in B-ALL patients, with lower POM121 expression (84%, 75% versus 54%, 46%, respectively), in T-ALL, in contrast, the OS results were better in patients with a higher POM121 expression (90%, 90% versus 60%, 60%, respectively). Patients with a higher POM121 expression than the mean of the control group and who had relapse and central nervous system involvement had statistically significantly lower OS results in the 3rd and 10th years (16%, 0% versus 84%, 78%, respectively).&#x0D; Conclusion: High POM121 expression negatively affects the prognosis in patients with ALL. This is a study to show the relationship between POM121 expression and prognosis in childhood acute lymphoblastic leukemias, POM121 function will be clarified further with more comprehensive studies.

Clonal origin and development of high hyperdiploidy in childhood acute lymphoblastic leukaemia

High hyperdiploid acute lymphoblastic leukemia (HeH ALL), one of the most common childhood malignancies, is driven by nonrandom aneuploidy (abnormal chromosome numbers) mainly comprising chromosomal gains. In this study, we investigate how aneuploidy in HeH ALL arises. Single cell whole genome sequencing of 2847 cells from nine primary cases and one normal bone marrow reveals that HeH ALL generally display low chromosomal heterogeneity, indicating that they are not characterized by chromosomal instability and showing that aneuploidy-driven malignancies are not necessarily chromosomally heterogeneous. Furthermore, most chromosomal gains are present in all leukemic cells, suggesting that they arose early during leukemogenesis. Copy number data from 577 primary cases reveals selective pressures that were used for in silico modeling of aneuploidy development. This shows that the aneuploidy in HeH ALL likely arises by an initial tripolar mitosis in a diploid cell followed by clonal evolution, in line with a punctuated evolution model.

Contributions of ARID5B, IKZF1, PIP4K2A, and GATA3 Gene Polymorphisms to Childhood Acute Lymphoblastic Leukemia in a Chinese Population.

Various studies have shown that single nucleotide polymorphisms in the AT-rich interaction domain 5B (ARID5B), IKAROS family zinc finger 1 (IKZF1), phosphatidylinositol-5-phosphate 4-kinase type 2 alpha (PIP4K2A), and GATA binding protein 3 (GATA3) genes may be associated with the susceptibility and prognosis of childhood acute lymphoblastic leukemia (ALL). The present study aimed to investigate the association of ARID5B rs10821936, IKZF1 rs4132601, PIP4K2A rs7088318, and GATA3 rs3824662 gene polymorphisms with the susceptibility and prognosis of childhood ALL in China. We found that the C allele of rs10821936 (ARID5B) and the A allele of rs3824662 (GATA3) were associated with an increased risk of childhood ALL in the Chinese population. There was no significant difference in frequencies of rs4132601 (IKZF1) and rs7088318 (PIP4K2A) genotypes and alleles between the childhood ALL and control groups. We observed that CC genotype of rs10821936 (ARID5B) was associated with increased rates of high-risk and moderate-risk childhood ALL. The rs10821936 (ARID5B) could serve as a potential biomarker for assessing the risk of childhood ALL in Chinese children.

A New Case of Childhood Acute Lymphoblastic B-Cell Leukemia from Pristina

Abstract Acute lymphoblastic leukemia (ALL) is a malignant disease caused by mutations in B- or T-cell precursors of bone marrow cells. Childhood acute lymphoblastic leukemia (ALL) is a subtype of pediatric cancer with a 1 in 2000 incidence. Here we present a new childhood ALL in a 3-year-old girl. As CD45/19, CD10/19, CD3, CD8, CD10, and CD19 were positive in immunohistochemically analyses of blast cells, a B-ALL was diagnosed with a causative ETV6-RUNX1 gene fusion. The patient was treated based on standard protocols BMF-ALL 2009. Interestingly, an aunt and a grandfather of the patient had experienced malignancies as well, which may be carefully interpreted as a hint on a familial cancer syndrome.

Yeni Tanı Pediatrik Akut Lenfoblastik Lösemide, Kemik İliği Biyopsisinde İmmünohistokimyasal Bulguların Akım Sitometrik Bulgular ile İlişkisinin Değerlendirilmesi

Background and objectives: The development of new therapeutic options to treat leukemia (therapies targeting chimeric antigen receptor [CAR] T cells) down-regulates markers expressed on the cell surface. Therefore, conventional immunophenotyping panels no longer make these antigens unreliable for identifying a B cell immunophenotype. In our study, we methodically compared multiparametric flow cytometry (FC) in bone marrow aspiration and immunohistochemical (IHC) analysis in bone marrow biopsy in childhood acute lymphoblastic leukemia (ALL). We sought to answer whether these two methods could be alternatives to each other in the diagnosis of leukemia. &#x0D; Material-Method: Twenty-eight patients diagnosed with ALL were included in the study. A Kappa test was performed between the expression rates of the antibodies studied in simultaneous FC and IHC studies in bone marrow aspiration and biopsy samples performed at the initial diagnosis. &#x0D; Results: Twenty-three of the patients were precursor B-ALL (BCP-ALL) and 5 were T-ALL. In the immunophenotyping of patients with BCP-ALL using FC and IHC, MPO, CD79A, CD14, CD3 expressions were the same, while CD19, CD7, CD117, CD33, CD 56, CD34 expressions were very good, good concordance for CD20 expressions and moderate for CD10 expressions. In immunophenotyping of patients diagnosed with T-ALL using FC and IHC, CD20, CD19, CD14, CD79a, MPO, CD22 expressions were the same and excellent agreement was found in terms of CD2, CD10, CD34 expressions. &#x0D; Conclusion: In cases where there are treatments that affect immunophenotyping, costly methods such as FC are not available, or bone marrow aspiration cannot be taken adequately, immunophenotyping with IHC can be safely performed in the diagnosis of pediatric ALL in bone marrow biopsy.