Acute leukemias with complex karyotype show a similarly poor outcome independent of mixed, myeloid or lymphoblastic immunophenotype: A study from the Bone Marrow Pathology Group

Kirtek, Timothy; Chen, Weina; Laczko, Dorottya; Bagg, Adam; Koduru, Prasad; Foucar, Kathryn; Venable, Emily M.; Nichols, Meredith M.; Rogers, Heesun J.; Orazi, Attilio; Hsi, Eric D.; Wang, Sa A.; Arber, Daniel A.; Weinberg, Olga K.

doi:10.1016/j.leukres.2023.107309

Cited by 3 publications

(2 citation statements)

References 24 publications

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“…The 5th Edition of the WHO Classification, ICC, and some other studies advocate that ALAL (including AUL) with myelodysplastic syndrome defining cytogenetics/genetic abnormalities be classified as AML-MR, as exemplified in this case. 1,2,5, 6 We believe this is the first reported case of AML-MR masquerading as AUL with CD43 expression.…”

mentioning

confidence: 72%

Acute Myeloid Leukemia with Myelodysplasia-related Cytogenetic/Genetic-defined Abnormalities Masquerades as Acute Undifferentiated Leukemia

Xu,

Mueller

2024

Gene Expr

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A 71-year-old man was admitted for complete heart block and anemia, neutropenia with more than 15% undifferentiated-looking blasts. He had no prior hematological diseases. He had approximately 100 lbs of weight loss during the last year. The computed tomography scan of chest, abdomen, and pelvis showed no lymphadenopathy or splenomegaly. Blood tests showed: leukocytes, 8.9 × 10 9 /L; neutrophils, 1.34 × 10 9 /L; blasts, 1.83 × 10 9 /L; hemoglobin, 71 g/L; mean corpuscular volume, 90.9 fL; platelets, 489 × 10 9 /L, reticulocytes 77 × 10 9 /L. Peripheral blood (PB) film demonstrated more than 20% of blasts. The blasts were of medium to large size, with a high nuclear/cytoplasm (N/C) ratio, open chromatin, and conspicuous nucleoli. In addition, dysplastic granulocytes were present (hypo-granular neutrophils/bands). The bone marrow aspirate revealed hypercellular bone marrow with over 70% blasts, which had a high N/C ratio and conspicuous nucleoli. No obvious Auer rods were observed. Megakaryopoiesis was markedly dysplastic with mono/hypo-lobated megakaryocytes and those with separate lobes (Fig. 1a, May-Grunwald-Giemsa stain, original magnification × 40, red arrows). Granulopoiesis and erythropoiesis were suppressed but mild dysplastic features could be observed including hypo-granular neutrophils and bands and dysplastic erythropoiesis including irregular nuclear contour, karyorrhexis, poor hemoglobinization, etc. No obvious lymphocytosis, plasma cells, or non-hematopoietic cells were observed. Flow cytometry immunophenotyping of the bone marrow aspirate illustrated that the blasts were positive for CD34 + , Tdt + , HLA-DR + , partial cCD79a +/− and partial CD36 +/− , but were negative for CD117

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confidence: 72%

Acute Myeloid Leukemia with Myelodysplasia-related Cytogenetic/Genetic-defined Abnormalities Masquerades as Acute Undifferentiated Leukemia

Xu,

Mueller

2024

Gene Expr

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“…RNA changes in regulation can lead to cell cycle arrest and apoptosis. Mutations in the genes controlling RNA regulation, SF3B1 (Spicing factor 3b subunit2) , SFSF2 (Serine and arginine rich splicing factor 2) , and IKZF1 ( IKAROS family finger 1 ) have been described and may affect these processes in myeloid cancers including MPN ( 14 , 15 ).…”

Section: Epigeneticsmentioning

confidence: 99%

Epigenetics in myeloproliferative neoplasms

Greenfield

McMullin

2023

Front. Oncol.

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The myeloproliferative neoplasms (MPNs) are a group of acquired clonal disorders where mutations drive proliferative disease resulting in increased blood counts and in some cases end-stage myelofibrosis. Epigenetic changes are the reversible modifications to DNA- and RNA-associated proteins that impact gene activity without changing the DNA sequence. This review summarizes mechanisms of epigenetic changes and the nucleosome. The drivers and epigenetic regulators in MPNs are outlined. In MPNs, distinct patterns of epigenetic dysregulation have been seen in chronic and in advanced phases. Methylation age and histone modification are altered in MPNs and by further treatment. The alterations found in methylation age in MPNs and with treatment are discussed, and the changes in histone modification with Janus kinase (JAK) inhibition are evaluated. Currently available therapeutic areas where the epigenome can be altered are outlined. Thus, we review the current knowledge and understanding of epigenetics in MPN and consider further management options. Understanding the epigenome and its alteration in MPNs and epigenetic changes associated with the progression of disease will lead to advances in therapeutic options.

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Acute myeloid leukemia with mixed phenotype is characterized by stemness transcriptomic signatures and limited lineage plasticity

Galera,

Dilip,

Derkach

et al. 2023

Preprint

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Mixed phenotype (MP) in acute leukemias poses unique classification and management dilemmas and can be seen in entities other than de novo mixed phenotype acute leukemia (MPAL). Although WHO classification empirically recommends excluding AML with myelodysplasia related changes (AML-MRC) and therapy related AML (t-AML) with mixed phenotype (AML-MP) from MPAL, there is lack of studies investigating the clinical, genetic, and biologic features of AML-MP. We report the first cohort of AML-MRC and t-AML with MP integrating their clinical, immunophenotypic, genomic and transcriptomic features with comparison to MPAL and AML-MRC/t-AML without MP. Both AML cohorts with and without MP shared similar clinical features including adverse outcomes but were different from MPAL. The genomic landscape of AML-MP overlaps with AML without MP but differs from MPAL. AML-MP harbors more frequentRUNX1mutations than AML without MP and MPAL.RUNX1mutations did not impact the survival of patients with MPAL. Unsupervised hierarchal clustering based on immunophenotype identified biologically distinct clusters with phenotype/genotype correlation and outcome differences. Furthermore, transcriptomic analysis showed an enrichment for stemness signature in AML-MP and AML without MP as compared to MPAL. Lastly, MPAL but not AML-MP often switched to lymphoid only immunophenotype after treatment. Expression of transcription factors critical for lymphoid differentiation were upregulated only in MPAL, but not in AML-MP. Our study for the first time demonstrates that AML-MP clinically and biologically resembles its AML counterpart without MP and differs from MPAL, supporting the recommendation to exclude these patients from the diagnosis of MPAL. Future studies are needed to elucidate the molecular mechanism of mixed phenotype in AML.Key pointsAML-MP clinically and biologically resembles AML but differs from MPAL.AML-MP showsRUNX1mutations, stemness signatures and limited lymphoid lineage plasticity.

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Acute leukemias with complex karyotype show a similarly poor outcome independent of mixed, myeloid or lymphoblastic immunophenotype: A study from the Bone Marrow Pathology Group

Cited by 3 publications

References 24 publications

Acute Myeloid Leukemia with Myelodysplasia-related Cytogenetic/Genetic-defined Abnormalities Masquerades as Acute Undifferentiated Leukemia

Acute Myeloid Leukemia with Myelodysplasia-related Cytogenetic/Genetic-defined Abnormalities Masquerades as Acute Undifferentiated Leukemia

Epigenetics in myeloproliferative neoplasms

Acute myeloid leukemia with mixed phenotype is characterized by stemness transcriptomic signatures and limited lineage plasticity

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