Defining 2 biologically and clinically distinct groups in acute leukemia with a mixed phenotype Journal Article
| Authors: | Galera, P.; Dilip, D.; Derkach, A.; Chan, A.; Zhang, Y.; Persaud, S.; Mishra, T.; Kramer, K.; Kathpalia, M.; Liu, Y.; Famulare, C.; Gao, Q.; Mata, D. A.; Arcila, M.; Geyer, M. B.; Stein, E.; Dogan, A.; Roshal, M.; Levine, R. L.; Glass, J.; Xiao, W. |
| Article Title: | Defining 2 biologically and clinically distinct groups in acute leukemia with a mixed phenotype |
| Abstract: | A mixed phenotype (MP) is a characteristic of de novo MP acute leukemia (MPAL), but it can also be found in other leukemias. It poses substantial classification and management dilemmas. Herein, we report a large cohort of acute leukemia with MP and define acute myeloid leukemia with MP (AML-MP) and MPAL as 2 distinct groups by characterizing clinical, genetic, and transcriptomic features. Clinically, patients with AML-MP and MPAL were both treated with either AML- or acute lymphoblastic leukemia (ALL)–directed induction regimens. AML-MP has inferior responses (hazard ratio, 12.5; 95% confidence interval, 2.72-57.8; P = .001), whereas MPAL has better responses to ALL-directed treatment. Genetically, AML-MP harbors more frequent RUNX1 (23/52 [44%]) and TP53 (12/52 [23.1%]) mutations. In contrast, RUNX1 mutations are less frequent in MPAL (8/35 [23%]; P = .01 vs AML-MP) and TP53 mutations as a driver are virtually absent in MPAL. Transcriptionally, AML-MP shows enrichment for stemness signatures and a relative deficit of transcription factors critical for myeloid and lymphoid differentiation. Furthermore, AML-MP rarely switches to a lymphoid immunophenotype after treatment, in contrast to MPAL (1/40 [2.5%] vs 10/28 [35.7%]; P = .0003). Last, a genomic classification framework is proposed for future studies. Together, these data support the designation of AML-MP as a diagnosis distinct from MPAL and provide novel insights into the pathogenesis and therapies of acute leukemia with MP. © 2025 American Society of Hematology |
| Journal Title: | Blood |
| Volume: | 145 |
| Issue: | 18 |
| ISSN: | 0006-4971 |
| Publisher: | American Society of Hematology |
| Date Published: | 2025-05-01 |
| Start Page: | 2056 |
| End Page: | 2069 |
| Language: | English |
| DOI: | 10.1182/blood.2024026273 |
| PUBMED: | 39813682 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | The MSK Cancer Center Support Grant (P30 CA008748) is acknowledge in the PDF -- Corresponding authors is MSK author: Wenbin Xiao and Jacob Glass -- Source: Scopus |
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