Myeloid/lymphoid precursor cell neoplasms and mixed phenotype acute leukemias: A Bone Marrow Workshop Report from the 22nd European Association for Hematopathology/Society of Hematopathology Meeting, Dubrovnik, 2024.

[OBJECTIVES] The bone marrow workshop (session 3), held at the 22nd Meeting of the European Association for Hematopathology/Society of Hematopathology in Dubrovnik, was dedicated to myeloid/lymphoid precursor cell neoplasms and mixed-phenotype acute leukemias (MPALs). We hereby report the clinicopathologic, immunophenotypic, and genetic features of the submitted cases.

[METHODS] The workshop report includes 55 cases; 37 cases represented acute myeloid leukemia (AML) and acute leukemia of ambiguous lineage. Other cases included blast phase of chronic myeloid leukemia (CML), myeloid/lymphoid neoplasms with TK gene fusions (M/LN-TK), and myelodysplastic syndrome (MDS). Additionally, cases of early T-precursor lymphoblastic leukemia (ETP-ALL) and B-precursor lymphoblastic leukemia (B-ALL) were reviewed.

[RESULTS] Among acute leukemia cases, 4 of 8 with the undifferentiated phenotype were reclassified as AML, myelodysplasia related (AML-MR) due to the presence of MDS-related gene mutations or complex karyotype. Thirteen of 20 MPAL cases were reclassified as AML-MR and/or AML with mutated TP53 (fifth edition of the World Health Organization classification/International Consensus Classification). Two cases had complex karyotypes and TP53 mutations, manifesting in the postcytotoxic treatment setting. TP53 mutations were absent in immunophenotypically defined MPAL and in MPAL with BCR::ABL1. Mixed phenotypes were also described in the blast phase of M/LN-TK, CML, and MDS.

[CONCLUSIONS] Mixed phenotype is frequently identified in AML-MR. Future studies are needed to clarify how cases with MR gene mutations and TP53 mutations should be best classified. Additionally, MPAL, T/myeloid, and ETP-ALL and some genetically defined MPAL, B/myeloid, and B-ALL show phenotypic/genetic overlap and are challenging to diagnose. A genomic classification framework is proposed to separate AML-MR and precursor lymphoid neoplasms from MPAL.