B/T mixed phenotype acute leukemia revealing immunophenotypic lineage-genotype associations and frequent myelodysplasia-related cytogenetic/gene abnormalities: implication for diagnosis and treatment.

B/T mixed-phenotype acute leukemia (MPAL) is a rare subtype of leukemia with diagnostic and therapeutic challenges due to its rarity, genomic diversity, and evolving diagnostic criteria. We report six cases of B/T MPAL with clinicopathological and genomic characterization. Most cases (5/6) demonstrated immunophenotypic/lineage-genotype-associations, i.

Differential diagnosis of multiple myeloma.

Distinguishing multiple myeloma from B-cell lymphomas can be a diagnostic challenge. There can be significant morphologic, immunophenotypic and clinical overlap that may require additional molecular genetic ancillary studies and careful clinical review to render an accurate diagnosis. The focus of this review will be on the differential diagnosis of multiple myeloma with an emphasis on low-grade B-cell lymphomas with plasmacytic differentiation and aggressive B-cell lymphomas with plasmablastic morphology that can mimic true plasma cell neoplasms.

Trisomy 8 in De Novo Acute Myeloid Leukemia Lacking MDS-Related Cytogenetics Does Not Significantly Influence Survival.

Introduction: The 2022 WHO and ICC classifications identify MDS-related cytogenetic abnormalities and secondary gene mutations (SM) that in de novo disease are diagnostic of myelodysplasia-related AML, which confers a poorer prognosis. While most MDS-related abnormalities overlap between the two classifications, trisomy 8 (+8) is unique to the ICC and has not been previously included as an MDS-related abnormality. In light of this, we sought to determine the prognostic significance of +8 as an MDS-related abnormality in patients with de novo AML lacking other MDS-related cytogenetics.

Investigation of NPM1 mutation frequency in cutaneous blastic plasmacytoid dendritic cell neoplasms.

Background: Blastic plasmacytoid dendritic cell neoplasm (BPDCN) and acute myeloid leukemia (AML) show overlapping clinicopathological presentations, which makes it challenging to differentiate on a small skin biopsy. NPM1 mutations are the most common genetic lesions in AML, accounting for one third of cases and cause an aberrant cytoplasmic delocalization of NPM1 mutants, which can be detected by an immunohistochemical stain. Frequency of NPM1 mutations in BPDCN remains controversial.

Imatinib-Induced Clinical Response in ETV6::ACSL6 Myeloid Neoplasm with Eosinophilic Pneumonitis: A Case Report.

BACKGROUND Myeloid neoplasms with [em]ETV6::ACSL6[/em] fusions are extremely rare entities that are characterized by eosinophilic and/or basophilic leukocytosis. While they clinically mimic myeloid neoplasms with eosinophilia and tyrosine kinase fusions such as [em]ETV6::PDGFRB[/em], they have not been shown to be responsive to imatinib. There are currently no effective treatments available and clinical outcomes are poor.

Genomic Landscape of Mixed Phenotype Acute Leukemia Associated With Immunophenotypic Lineage Predominance: Impact on Diagnosis and Treatment.

Objectives: Mixed phenotype acute leukemia (MPAL) often poses challenges in diagnosis and clinical management. This is the first study to assess the lineage/immunophenotype-genotype association and the significance of AML-myelodysplasia-related changes (MR, cytogenetic abnormalities and gene mutations, AML-MR-CG-Gene) in MPAL classification.

Methods: We conducted a clinicopathologic and genomic evaluation of 25 MPAL cases by the WHO-HEM5/ICC classification criteria, except for retaining those MPAL cases with AML-MR-CG-Gene (Conditional-MPAL).

Real world efficacy of luspatercept in patients with lower-risk myelodysplastic syndromes/neoplasms (MDS); a single center study in a heavily pretreated cohort.

Anemia leads to transfusion dependence and decreases quality of life in LR-MDS patients. Our study retrospectively evaluates the efficacy and safety of luspatercept in the real-world treatment of anemia in LR-MDS, and the impact of patient and disease characteristics on hematologic improvement erythroid (HI-E). Baseline patient and disease characteristics, and transfusion burden (TB) were captured.

Genomic and Clinicopathological Characterization of CRLF2-Rearranged Mixed Phenotype Acute Leukemia.

Rearrangements of cytokine receptor-like factor 2 gene (CRLF2) are present in ∼50% of B-lymphoblastic leukemia/lymphoma (B-ALL) with BCR::ABL1-like features. Herein, we report three patients with CRLF2-rearranged mixed phenotype acute leukemia (MPAL). All three cases were B/myeloid MPAL in young patients harboring P2RY8::CRLF2 or IGH::CRLF2 with additional genomic alterations in signaling (JAK and RAS) and cell cycle (CDKN2A/B) pathways, a genomic profile similar to that in BCR::ABL1-like B-ALL.

Impact of myelodysplasia-related mutations on 2022 European LeukemiaNet genetic risk classification in de novo acute myeloid leukemia with normal karyotype.

De novo normal karyotype AML 2017ELN and 2022ELN Genetic Risk Category Changes and Overall Survival in Induction Treated Patients.

Presence but not number of secondary type mutations influences outcome in de novo AML without MDS-associated or recurring cytogenetic abnormalities.

A group of gene mutations has been identified to be strongly associated with secondary acute myeloid leukemias (AML) arising from prior myeloid neoplasms. The International Consensus Classification (ICC) and proposed 5th edition of the World Health Organization (WHO) classification differ by inclusion of . A recent study suggested that having two or more secondary mutations is associated with a particularly poor prognosis.

Updates in molecular genetics of therapy-related myeloid neoplasms.

Therapy-related myeloid neoplasms (t-MN) are a heterogeneous group of aggressive myeloid neoplasms that arise following exposure to various cytotoxic therapeutic agents and/or ionizing radiation for treatment of prior non-myeloid malignancy or autoimmune disease. Each therapeutic group has been associated with varying latency intervals from the time of therapy exposure to onset of t-MN, as well as certain recurrent genetic alterations. This review will focus on the molecular genetic alterations that have been described in t-MNs, as well as recent updates regarding diagnostic classification.

Clinicopathologic and Molecular Analysis of Normal Karyotype Therapy-Related and De Novo Acute Myeloid Leukemia: A Multi-Institutional Study by the Bone Marrow Pathology Group.

Purpose: Therapy-related acute myeloid leukemias (t-AML) are a heterogenous group of aggressive neoplasms that arise following exposure to cytotoxic chemotherapy and/or ionizing radiation. Many therapy-related myeloid neoplasms (t-MN) are associated with distinct chromosomal aberrations and/or alterations, but little is known about the clinicopathologic and molecular features of normal karyotype t-AML (NK-t-AML) and whether this t-MN subtype is distinctly different from NK de novo AML (NK-dn-AML).

Methods: This multi-institutional study by the Bone Marrow Pathology Group retrospectively evaluated clinicopathologic and molecular characteristics of 335 patients with NK-AML, comprising 105 t-AML and 230 dn-AML cases.

Comparison of therapy-related and de novo core binding factor acute myeloid leukemia: A bone marrow pathology group study.

This multi-institutional study retrospectively evaluated clinicopathologic and genetic characteristics in 351 patients with core-binding-factor acute myeloid leukemia (CBF-AML), comprising 69 therapy-related (t-CBF-AML) and 282 de novo cases. The T-CBF-AML patients were older, had lower WBC counts, and slightly higher hemoglobin than patients with de novo disease. Secondary cytogenetic abnormalities were more frequent in patients with de novo disease than t-CBF-AML (57.

The Clinical Utility of the Genomic Prostate Score in Men with Very Low to Intermediate Risk Prostate Cancer.

Purpose: We retrospectively investigated the Genomic Prostate Score® assay in clinical practice at an urban tertiary care academic center.

Materials And Methods: We reviewed all Genomic Prostate Score results acquired during a 3-year period. Changes in patient NCCN® (National Comprehensive Cancer Network®) risk group, including very low, low, intermediate or high risk, and ultimate management decisions were recorded.