Diagnosis Of Leukemia Research Articles

The importance of targeted next-generation sequencing based genomic profiling at diagnosis of childhood acute myeloid leukemia: a single center experience

Background. The management of pediatric acute myeloid leukemia (AML) is based on the prognostic risk classification of initial leukemia. Targeted next-generation sequencing (NGS) is a reliable method used to identify recurrently mutated genes of pediatric AML and associated prognosis. Methods. In this study, we retrospectively evaluated the prognostic, and therapeutic utility of a targeted NGS panel covering twenty-five genes, in 21 children with de novo and 8 with relapsed or secondary AML. Results. Variants were detected in 44.8% of patients, and 63.2% of them were in the signaling pathway genes. The number of variants per patient and diversity increased with age. The panel results affected hematopoietic stem cell transplantation decisions, especially in core binding factor AML, and allowed the categorization of diseases according to current classifications. Panel results also pointed out predisposition to germline leukemia to the extent of the panel coverage. No targeted therapy was used based on the variants, and none of the variants were used to monitor minimal residual disease. Conclusions. Targeted NGS results, along with well-known genetic aberrations and treatment responses, can guide treatment modalities. The coverage of the routine panels should include proven mutations of childhood AML and germline leukemia predisposition genes.

Machine Learning-Based Prediction of Blood Stream Infection in Pediatric Febrile Neutropenia.

This study aimed to develop machine learning (ML) prediction models for identifying bloodstream infection (BSI) and septic shock (SS) in pediatric patients with cancer who presenting febrile neutropenia (FN) at emergency department (ED) visit. A retrospective study was conducted on patients, aged younger than 18 years, who visited a tertiary university-affiliated hospital ED due to FN between January 2004 and August 2022. ML models, based on XGBoost, were developed for BSI and SS prediction. After applying the exclusion criteria, we identified 4423 FN events during the study period. We identified 195 (4.4%) BSI and 107 (2.4%) SS events. The BSI and SS models demonstrated promising performance, with area under the receiver operating characteristic curve values of 0.87 and 0.88, respectively, which were superior to those of the logistic regression models. Clinical features, including body temperature, some laboratory results, vital signs, and diagnosis of acute myeloblastic leukemia were identified as significant predictors. The ML-based prediction models, which use data obtainable at ED visits may be valuable tools for ED physicians to predict BSI or SS.

Cell Nuclear Segmentation of B-ALL Images Based on MSFF-SegNeXt.

The diagnosis and treatment of B-Lineage Acute Lymphoblastic Leukemia (B-ALL) typically rely on cytomorphologic analysis of bone marrow smears. However, traditional morphological analysis methods require manual operation, leading to challenges such as high subjectivity and low efficiency. Accurate segmentation of individual cell nuclei is crucial for obtaining detailed morphological characterization data, thereby improving the objectivity and consistency of diagnoses. To enhance the accuracy of nucleus segmentation of lymphoblastoid cells in B-ALL bone marrow smear images, the Multi-scale Feature Fusion-SegNeXt (MSFF-SegNeXt) model is hereby proposed, building upon the SegNeXt framework. This model introduces a novel multi-scale feature fusion technique that effectively integrates edge feature maps with feature representations across different scales. Integrating the Edge-Guided Attention (EGA) module in the decoder further enhances the segmentation process by focusing on intricate edge details. Additionally, Hamburger structures are strategically incorporated at various stages of the network to enhance feature expression. These combined innovations enable MSFF-SegNeXt to achieve superior segmentation performance on the SN-AM dataset, as evidenced by an accuracy of 0.9659 and a Dice coefficient of 0.9422. The results show that MSFF-SegNeXt outperforms existing models in managing the complexities of cell nucleus segmentation, particularly in capturing detailed edge structures. This advancement offers a robust and reliable solution for subsequent morphological analysis of B-ALL single cells.

The Clinical Impact of NPM1 Mutations and the Effect of Concurrent Mutations in Acute Myeloid Leukemia: Unraveling the Prognostic Significance.

Nucleophosmin (NPM1) gene mutations occur in approximately 30%-35% of individuals with an initial diagnosis of acute myeloid leukemia (AML). Mutations in this gene have been reported in 50%-60% of AML patients with a normal karyotype. These mutations help to distinguish clinicopathological and molecular features, setting them apart as a unique subset within the heterogeneous landscape of AML. In the present study, we investigated the frequency and clinical impact of NPM1 mut in 100 newly diagnosed adult Syrian patients with AML-normal karyotype (NK) using direct sequencing. We analyzed 100 AML-NK patients using direct sequencing to assess the prevalence and clinical impact of NPM1 mutations, as well as the co-occurrence of FLT3-ITD and DNMT3A mutations. Our results revealed that the prevalence of NPM1 mut was 22% among the patients; 86.4% of these mutations were type A (NM_002520.5:c.860-863dupTCTG), while 13.6% were de novo mutations (c.863_864insCCTG, p.Trp288CysfsTer12), (c.861_862dup, p.Trp288SerfsTer13), and (c.863_864insCCGG, p.Trp288CysfsTer12). Among our patients, 22% exhibited NPM1 mut, with 7% also harboring FLT3-ITD mut and 2% having DNMT3A mut. The presence of NPM1 mut was correlated with a statistically significant increase in bone marrow blast percentage (p = 0.017). Notably, patients with NPM1 mut displayed significantly higher mortality rates, with 72.7% succumbing to the disease compared to 29.5% of patients without NPM1 mut (p < 0.001). Furthermore, our results showed that when the overall survival (OS) time exceeded 8.35 months, the likelihood of NPM1 wild-type status was greater. The evaluation of NPM1 mut and co-mutation has consistently demonstrated remarkable prognostic significance in AML, suggesting the potential for improved response rates, extended disease-free periods, and OS. Our findings provide valuable insights for understanding molecular leukemogenesis in AML-NK patients and will aid in clinical diagnosis, prognostic implications, and the development of targeted therapy strategies for Syrian AML patients.

Unveiling The Shadows: A Guide For Diagnosing Leukemia And Better Outcome

Diagnosis of leukemia is performed through blood tests and a bone marrow diagnostic assay, with blood cell counts playing a critical role in the healthcare industry. Traditionally, hospital laboratories manually count blood cells using a hemocytometer. This approach is tedious, prone to errors, and time- consuming. The research introduces a fully automated method for identifying various types of leukemia and detecting nursing platelets in blood samples. This proposed technique employs a multi-class classifier to overcome the limitations and missed opportunities often encountered with traditional cell classification methods. This technique employs geographical metrics to identify various color feature statistics within the context of supervised machine learning. The model, trained and validated using several machine learning approaches, achieves an accuracy of 92%.

Identification of a Novel RUNX1::STX2 Fusion in Mixed-Phenotype Acute Leukemia (MPAL) With BCR::ABL1.

Mixed phenotype acute leukemia (MPAL) is a rare type of acute leukemia (AL), MPAL with BCR::ABL1 fusion is the main subtype of MPAL, mainly affecting adult males. It is an acute leukemia with unique clinical and biological characteristics that involve both the myeloid and lymphatic systems. Gene fusion plays a crucial role in the pathogenesis, diagnosis, prognosis assessment, and treatment of leukemia. We present the first discovery of a novel fusion of RUNX1::STX2 in this subtype, which is co-expressed with BCR::ABL1 fusion. RUNX1 is a crucial transcription factor for hematopoietic differentiation, frequently found to be abnormal in AML, while STX2 may play a role in cancer progression. The RUNX1::STX2 fusion protein may act as the primary negative regulator of wild-type RUNX1, influencing normal cell differentiation and proliferation, consequently elevating the risk of leukemia. The gene fusion status of this patient is unique and complex, requiring further exploration to understand its functional significance in leukemia progression and treatment response.

Diagnosis and typing of leukemia using a single peripheral blood cell through deep learning

AbstractLeukemia is highly heterogeneous, meaning that different types of leukemia require different treatments and have different prognoses. Current clinical diagnostic and typing tests are complex and time‐consuming. In particular, all of these tests rely on bone marrow aspiration, which is invasive and leads to poor patient compliance, exacerbating treatment delays. Morphological analysis of peripheral blood cells (PBC) is still primarily used to distinguish between benign and malignant hematologic disorders, but it remains a challenge to diagnose and type these diseases solely by direct observation of peripheral blood(PB) smears by human experts. In this study, we apply a segmentation‐based enhanced residual network that uses progressive multigranularity training with jigsaw patches. It is trained on a self‐built annotated dataset of 21,208 images from 237 patients, including five types of benign white blood cells(WBCs) and eight types of leukemic cells. The network is not only able to discriminate between benign and malignant cells, but also to typify leukemia using a single peripheral blood cell. The network effectively differentiated acute promyelocytic leukemia (APL) from other types of acute myeloid leukemia (non‐APL), achieving a precision rate of 89.34%, a recall rate of 97.37%, and an F1 score of 93.18% for APL. In contrast, for non‐APL cases, the model achieved a precision rate of 92.86%, but a recall rate of 74.63% and an F1 score of 82.75%. In addition, the model discriminates acute lymphoblastic leukemia(ALL) with the Ph chromosome from those without. This approach could improve patient compliance and enable faster and more accurate typing of leukemias for early diagnosis and treatment to improve survival.

ClearLLab 10C reagents panel can be applied to analyze paucicellular samples by flow cytometry.

The FDA-approved ClearLLab 10C Reagents Panel (Beckman Coulter) simplified the diagnosis of leukemias and lymphomas by flow cytometry. However, the requirement of using 3 × 106 cells/mL cannot be met for paucicellular samples. Therefore, we tested whether this 10-color panel can be reliably employed to analyze specimens with low cell concentrations. Serial dilutions of 16 samples (5 normal, 11 abnormal), yielding concentrations ranging from 3.0 × 106 to 0.0469 × 106 cells/mL (64-fold difference), were stained using the B-cell and T-cell panels of the ClearLLab 10C system, and mean fluorescence intensity (MFI) was measured for each antibody. For each cell dilution, the deviation from the value obtained with the FDA-approved concentration of 3.0 × 106 cells/mL was calculated. The agreement between the highest and lowest cell concentration data was evaluated by the Bland and Altman method, Pearson's and Spearman's correlation analyses, and linear regression. In all patients, the antigen expression pattern was similar at all cell concentrations tested, and the mean deviation of the MFI from the value obtained using 3.0 × 106 cells/mL never exceeded 10% for any of the antibodies. The Bland-Altman method demonstrated the similarity between results obtained with the FDA-approved cell concentration and a 64-fold diluted cell suspension, and a high positive correlation was found between MFI acquired under these two conditions. The tests utilizing the lowest density of cells yielded the same patterns of antigen expression in all patients as those performed with the FDA-approved concentration, documenting a 100% concordance between these two protocols. The ClearLLab 10C panel can reliably determine the expression of markers of leukemias and lymphomas in paucicellular samples containing as little as 0.0469 × 106 cells/mL (64-fold lower than the FDA-approved concentration). This finding markedly expands the applicability of the ClearLLab 10C platform in a clinical setting.

Selinexor in combination with pomalidomide and dexamethasone for the treatment of primary plasma cell leukemia with 1q21+ abnormality: A case report.

Primary plasma cell leukemia is a rare and highly aggressive malignancy of the blood system, with rapid disease progression and a high early mortality rate. Currently, there is no recognized therapeutic regimen, leading to the adoption of strategies typically utilized for multiple myeloma, which, however, exhibit limited efficacy. Selinexor is considered effective in treating relapsed/refractory multiple myeloma, but there are currently no reports on its application in primary plasma cell leukemia. Here, we reported a case of primary plasma cell leukemia with multiple high-risk genetic factors (including 1q21+, 17p-, and 13q-) who received a chemotherapy regimen including selinexor, pomalidomide, and dexamethasone. This case was a 58-year-old male presenting with lower back pain, abdominal pain, and various systemic symptoms. The initial diagnosis of intestinal obstruction at a local hospital was followed by a referral to our emergency department due to abnormal blood test results indicative of a hematologic disorder. Further investigations confirmed a rare diagnosis of primary plasma cell leukemia of the IgA-k light chain subtype. The patient was promptly treated with a chemotherapy regimen comprising selinexor, pomalidomide, and dexamethasone in addition to supportive care. Subsequent assessments showed a significant response to treatment, with improvement in symptoms, normalization of blood parameters, and achievement of very good partial response. However, due to financial constraints, the patient declined hematopoietic stem cell transplantation and eventually opted to discontinue treatment, leading to disease progression. The combination of selinexor with pomalidomide and dexamethasone has shown good efficacy in primary plasma cell leukemia with high-risk genetic abnormalities. Our case may provide evidence for developing an effective selinexor-based regimen for treating primary plasma cell leukemia with high-risk genetic abnormalities.

The relationship between seasonality and the diagnosis of acute leukaemia in central South Africa

Background: Leukaemias are haematological malignancies resulting from the abnormal clonal proliferation of haematopoietic precursors. Their incidence is influenced by various environmental and genetic factors.Aim: With this retrospective descriptive study, the authors aimed to explore the possible influence of seasonality on the type and number of acute leukaemia (AL) diagnoses made at the Universitas Academic Hospital (UAH) National Health Laboratory Service (NHLS) from 01 January 2018 to 31 December 2021.Setting: Universitas Academic Hospital, Bloemfontein, South Africa.Methods: Archived laboratory reports of all patients diagnosed with lymphoid and myeloid during the study period were included. Patients’ age, sex, ethnicity, final diagnosis and date of diagnosis were recorded. Information was pseudonymised to maintain confidentiality. A descriptive statistical analysis was performed to explore the possible influence of seasonality on the number of cases and type of leukaemia diagnosed.Results: In all, 249 patients were included. Acute myeloid leukaemia (AML) was the most common AL subtype (n = 117; 47.0%). Over the 4-year study period, all AL subtypes were more frequently diagnosed in summer (n = 131; 52.6%). However, the monthly number of AL diagnoses was relatively consistent over the 4 years for all subtypes (p = 0.7603), with consistent peaks of AML cases during January and February (summer) and May (autumn).Conclusion: No statistically significant association between the different seasons and AL diagnosis was noted.Contribution: Further studies using a larger study population and a wider geographical area, conducted over a more extended period, might affect the observations made in this study

10-Year Real-World Data on Acute Myeloid Leukemia:

Introduction: Despite advances in Acute Myeloid Leukemia (AML) diagnosis and treatment, the outcomes in low- and middle-income countries (LMIC) are far apart from those in high-income countries (HIC). Objective: To describe the clinical features and outcomes of AML patients in Brazil's public health system, we conducted a retrospective analysis of all cases of non-promyelocytic AML diagnosed within 10 years (2007- 2017) in northeastern Brazil, Bahia. Methodology: We analyzed the real-life outcomes of 62 patients diagnosed with non-promyelocytic AML between 2007 and 2017 at a university hospital in Northeast Brazil. We classified patients using the European LeukemiaNet 2022 guideline into favorable (n=8), intermediate (n=18), and adverse risk (n=7) groups. Twenty-nine were not otherwise classified because no cytogenetic and/or molecular tests were available at diagnosis. Results: Allogeneic bone marrow transplant (alloBMT) was performed in 16 patients (37%). Median overall survival (mOS) was seven months. Among patients receiving alloBMT, mOS was 49 months, while for the chemotherapy group, it was six months (P = 0.003). For 10-year real-life data, we found complete remission of 53%, 5-year OS of 27%, and a mortality rate during induction therapy of 27%, inferior to HIC. Conclusion: Inferior outcomes found in LMIC result from a multifactorial scenario and an unmet need in the worldwide panorama of AML.

Fluorescent Aerolysin (FLAER) Binding Is Abnormally Low in the Clonal Precursors of Acute Leukemias, with Binding Particularly Low or Absent in Acute Promyelocytic Leukemia.

Flow cytometry plays a fundamental role in the diagnosis of leukemias and lymphomas, as well as in the follow-up and evaluation of minimally measurable disease after treatment. In some instances, such as in the case of acute promyelocytic leukemia (APL), rapid diagnosis is required to avoid death due to serious blood clotting or bleeding complications. Given that promyelocytes do not express the glycophosphatidylinositol (GPI)-anchored protein CD16 and that deficient CD16 expression is a feature of some CD16 polymorphisms and paroxysmal nocturnal hemoglobinuria (PNH), we included the GPI anchor probe FLAER aerolysin in the APL flow cytometry probe panel. Initial tests showed that FLAER binding was absent in pathological promyelocytes from APL patients but was consistently detected with high intensity in healthy promyelocytes from control bone marrow. FLAER binding was studied in 71 hematologic malignancies. Appropriate control cells were obtained from 16 bone marrow samples from patients with idiopathic thrombocytopenic purpura and non-infiltrated non-Hodgkin's lymphoma. Compared with the positive FLAER signal in promyelocytes from healthy bone marrow, malignant promyelocytes from APL patients showed weak or negative FLAER binding. The FLAER signal in APL promyelocytes was also lower than that in control myeloid progenitors and precursors from patients with other forms of acute myeloid leukemia (AML), B-cell acute lymphoblastic leukemia, or myelodysplastic syndrome. Minimal measurable disease studies performed in APL patients after treatment found normal promyelocyte expression when minimal measurable disease was negative and FLAER-negative promyelocytes when disease relapse was detected. The inclusion of FLAER in the flow cytometry diagnosis and follow-up of APL could be very helpful. Decreased FLAER binding was found in all cases of APL, confirmed by the detection of the PML-RARA fusion transcript and, to a lesser extent, in the other AMLs studied. This study also revealed FLAER differences in other acute leukemias and even between different precursors (myeloid and lymphoid) from healthy controls. However, the reason for FLAER's non-binding to the malignant precursors of these leukemias remains unknown, and future studies should explore the possible relation with an immune escape phenomenon in these leukemias.

Diagnosis and Treatment of Early T-Cell Precursor Acute Lymphoblastic Leukaemia (ETP-ALL)

Diagnosis and Treatment of Early T-Cell Precursor Acute Lymphoblastic Leukaemia (ETP-ALL)

Identification of Differentially Expressed Proteins As Potential Biomarkers for Diagnosis and Prognosis of Acute Myeloid Leukemia

Identification of Differentially Expressed Proteins As Potential Biomarkers for Diagnosis and Prognosis of Acute Myeloid Leukemia

The Effect of Mindfulness-Based Psychoeducation on Parental Psychology After Leukemia Diagnosis

This study’s purpose is to determine the effect of mindfulness-based psycho-education program for parents of children with leukemia on ruminative thought, perceived stress, and well-being. This experimental randomized controlled study was adopted with the parents of children. Mindfulness-based psychoeducation program was applied on online platform with parents. After the intervention, ruminative thinking styles, perceived stress levels and well-being levels of the parents in the experimental group were found to be significantly different from the control group (p < 0.05). The mindfulness-based psychoeducation program applied in this study was found to be effective in reducing ruminative thinking and perceived stress in parents of children diagnosed with leukemia. It was also concluded that the program was effective in maintaining parents’ level of well-being.

Combining array-assisted SERS microfluidic chips and machine learning algorithms for clinical leukemia phenotyping

The disease progression and treatment options of leukemia between different subtypes vary considerably, emphasizing the importance of phenotyping. However, early typing of leukemia remains challenging due to the lack of highly sensitive and specific analytical tools. Herein, we propose a SERS-based platform for the classification of acute lymphoblastic T-cell leukemia (T-ALL) and chronic myeloid leukemia (CML) through the combination of machine learning and microfluidic chips. The ordered arrays in microfluidic channels reshape the microscopic flow field and contacting interfaces, facilitating the uniform and efficient capture of tumor cells. To enable phenotypic analysis, spectrally orthogonal SERS aptamer nanoprobes were applied, providing composite spectral signatures of individual cells in accordance with surface protein expression. Further, machine learning algorithms were employed to analyze the SERS signatures automatically, resulting in an accuracy of 98.6 % for 73 clinical blood samples. The results demonstrate that this platform holds promising potential for clinical leukemia diagnosis and precision medicine.

Epigenetic features support the diagnosis of B-cell prolymphocytic leukemia and identify 2 clinicobiological subtypes

AbstractThe recognition of B-cell prolymphocytic leukemia (B-PLL) as a separate entity is controversial based on the current classification systems. Here, we analyzed the DNA methylome of a cohort of 20 B-PLL cases diagnosed according to the International Consensus Classification/World Health Organization HAEM4R guidelines, and compared them with chronic lymphocytic leukemia (CLL), mantle cell lymphoma (MCL), splenic marginal zone lymphoma (SMZL), and normal B-cell subpopulations. Unsupervised principal component analyses suggest that B-PLL is epigenetically distinct from CLL, MCL, and SMZL, which is further supported by robust differential methylation signatures in B-PLL. We also observe that B-PLL can be segregated into 2 epitypes with differential clinicobiological characteristics. B-PLL epitype 1 carries lower immunoglobulin heavy variable somatic hypermutation and a less profound germinal center–related DNA methylation imprint than epitype 2. Furthermore, epitype 1 is significantly enriched in mutations affecting MYC and SF3B1, and displays DNA hypomethylation and gene upregulation signatures enriched in MYC targets. Despite the low sample size, patients from epitype 1 have an inferior overall survival than those of epitype 2. This study provides relevant insights into the biology and differential diagnosis of B-PLL, and potentially identifies 2 subgroups with distinct biological and clinical features.

Convenient electrochemiluminescence biosensor for acute myeloid leukemia biomarker based on hyperbranched rolling circle amplification and vertically-ordered mesoporous silica film modified electrode

Vertically-ordered mesoporous silica film (VMSF), with large amount of small pores and abundant negative charges, had been modified on the surface of indium tin oxide electrodes and applied to develop an electrochemiluminescence (ECL) biosensor for acute myeloid leukemia biomarker hsa-miR-10a-5p (chosen as a model target). The small ECL indicator (Ru(phen)32+) can be enriched in the pores through electrostatic adsorption and then diffuse to the electrode surface to produce strong ECL signals. The presence of target can trigger hyperbranched rolling circle amplification (HRCA) and produce a large amount of double-stranded DNA (dsDNA). Ru(phen)32+ can embed into the groove structure of dsDNA and forms negatively charged large-sized complexes, which cannot pass through the narrow pores of VMSF to reach the electrode. This led to a significant decrease of ECL signal of the system. The change of the ECL intensity of the system had a linear relationship with logarithm of target concentration within the range of 1 fM–1 nM. The limit of detection was 1.23 fM. The developed biosensor had been applied to determine the target substance in serum samples with satisfied results without complicated sample pretreatment. The introduction of VMSF endows the biosensor with superior anti-interference capability and simpler operational steps, promising applications in the diagnosis of acute myeloid leukemia and potential extension to the analysis of other target molecules through primer design.

Utility of glass slide morphology (GSM) and whole slide image (WSI) in the diagnosis of acute leukemia (AL) by types

Utility of glass slide morphology (GSM) and whole slide image (WSI) in the diagnosis of acute leukemia (AL) by types

A Hypothesis for Diagnosis of Chronic Myeloid Leukemia based on miR-15a

Chronic myeloid leukemia (CML) is a type of leukemia characterized by myeloid proliferation. Morgana is a chaperone protein, whose levels are lower due to the overexpression of miR-15a in CP phase. By quantitatively detecting miR-15a and Morgana, we could verify the correlation of them to CP-CML, thus as biomarkers of CP-CML diagnosis.