Introduction Many new markers are being evaluated to increase the sensitivity and applicability of multicolor flow cytometry (MFC)‐based measurable residual disease (MRD) monitoring. However, most of the studies are limited to childhood B‐cell lymphoblastic leukemia/lymphoma (B‐ALL), and reports in adult B‐ALL are extremely scarce and limited to small cohorts. We studied the expression of CD304/neuropilin‐1 in a large cohort of adult B‐ALL patients and evaluated its practical utility in MFC‐based MRD analysis. Methods CD304 was studied in blasts from adult B‐ALL patients and normal precursor B cells (NPBC) from non‐B‐ALL bone marrow samples using MFC. CD304 expression intensity and pattern were studied with normalized‐mean fluorescent intensity (nMFI) and coefficient of variation of immunofluorescence (CVIF), respectively. MFC‐based MRD was performed at end of induction (EOI; day‐35), end of consolidation (EOC; day 78‐80), and subsequent follow‐up (SFU) time points. Results CD304 was positive in 120/214(56.07%) and was significantly associated with BCR‐ABL1 fusion (P = .001). EOI‐MRD and EOC‐MRD were positive in 129/214(60.3%) and 50/81(61.72%), respectively. CD304 was positive in a significant percentage of EOI (48%, 62/129) and EOC (52%, 26/50) MRD‐positive B‐ALL samples. Its expression was retained, lost, and gained in 73.7%, 26.3%, and 11.3% of EOI‐MRD and 85.7%, 14.3%, and none of EOC‐MRD samples, respectively. Low‐level MRD (<0.01%) was detectable in 34 of all (EOI + EOC + SFU = 189) MRD‐positive samples, and CD304 was found useful in 50% of these samples. Conclusion CD304 is commonly expressed in adult B‐ALL and clearly distinguish B‐ALL blasts from normal precursor B cells. It is a stable MRD marker and distinctly useful in the detection of MFC‐based MRD monitoring, especially in high‐sensitivity MRD assay.
Introduction: Myeloid neoplasm with blasts showing mast cell (MC)-differentiation and MC-component less than 10% of all nucleated cells but not fulfilling the criteria for systemic mastocytosis with associated hematological neoplasm (SM-AHN) or myelomastocytic leukemia (MML) has not been described in the literature. Herein, we report a study of diverse myeloid malignancies with blasts showing MCdifferentiation but not meeting the criteria for SM-AHN or MML. We also evaluated the utility of flow-cytometric immunophenotyping (FCI) in the characterization of immature-MCs (iMCs). Methods:We identified nine patients of myeloid neoplasms and studied their morphological, FCI, immunohistochemistry, cytogenetic and molecular characteristics.We also compared the immunophenotypic features of MCs from patient samples with control samples. Results:The study included patients with newly-diagnosed acute myeloid leukemia (n = 4), chronic myelomonocytic leukemia (n = 1), and chronic myeloid leukemia on follow-up (n = 4) showing MC differentiation in leukemic-blasts. These patients had mildly increased MCs (range, 0.5%-3%) in bone-marrow morphology, including immature-forms and did not meet the criteria for either SM-AHN or MML. On FCI, iMCs were positive for bright-CD117, heterogeneous-CD34, dim-to-negative-HLADR, and moderate-CD203c expression. Expression-levels of CD123 and CD38 were higher (p < 0.001) but CD33 and CD45 were lower in iMCs compared to mature-MC from control samples (p = 0.019 and p = 0.0037). Conclusion:We reported a rare finding of MC differentiation of leukemic blasts in diverse myeloid neoplasms and proposed it as a potential pre-myelomastocytic leukemia condition. We described the distinct immunophenotypic signature of immature-MCs using commonly used markers and highlighted the utility of FCI for the diagnosis of this entity.
Background: Multicolor flow cytometry-based DNA-ploidy (MFC-ploidy) analysis is a simple, sensitive, and popular method for ploidy analysis in B-cell acute lymphoblastic leukemia (B-ALL). However, the utility of MFC-ploidy in the detection of B-ALL with endoreduplication or masked hypodiploidy has not been reported. Herein, we studied the patterns of MFC-ploidy assessment and its utility to detect B-ALL with hypodiploidy and endoreduplication.Methods: MFC-ploidy analysis was performed using FxCycle Violet-dye-based method, and cytogenetic ploidy was evaluated using chromosomal-counting and FISH analysis. A total of 20 B-ALL cases with endoreduplication were studied for the patterns of MFC-ploidy analysis and compared with 250 patients with hyperdiploidy and 11 cases with pure hypodiploidy.Results: All B-ALL with endoreduplication revealed two distinct peaks (populations) on MFC-ploidy analysis: the first (hypodiploid) peak (median-DNA-index [DI], 0.82; range, 0.6-0.95) and the second (hyperdiploid) peak with almost twice DI (median-DI, 1.53; range, 1.14-1.75). Cytogenetic findings were available in 19 cases and confirmed hypodiploidy with endoreduplication in 13/19 (68.4%) and only hypodiploidy in 3/19 cases. The remaining three cases showed hyperdiploid blasts in cytogenetic studies. Of these three, two cases had <10% blasts population with hypodiploidy. Thus, masked-hypodiploidy could be diagnosed correctly in 3/19 cases on MFCploidy analysis.Conclusion: MFC-ploidy analysis shows a characteristic pattern of DNA-ploidy in samples with endoreduplication. It allows the distinction between samples with masked hypodiploidy from true hyperdiploidy. An integrated approach involving cytogenetic and MFC-ploidy detection is very helpful in the risk stratification of B-ALL in routine clinical practice.
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