Acute leukemia of ambiguous lineage, not otherwise specified with FLT3-ITD mutation and a possible origin in the common lymphoid progenitor

Abstract

The current major classification of acute leukemias is based on the assignment of cellular lineage to the blast population, for which an immunophenotypic analysis generally performed by multiparametric flow cytometry (FCM) is mandatory (Porwit & Béné, 2019). Furthermore, the phenotypic characterization of acute leukemias provides information about the pathogenesis of the disease, although it is sometimes difficult to correlate the blast population compartment with the normal stages of hematopoiesis. Acute leukemias of ambiguous lineage (ALAL) — category included in both the 5th edition of the World Health Organization Classification of Haematolymphoid Tumours (Khoury et al., 2022) and the International Consensus Classification of Myeloid Neoplasms and Acute Leukemias (Arber et al., 2022) — comprise a heterogeneous group of rare and aggressive diseases that includes acute undifferentiated leukemias (AUL) and mixedphenotype acute leukemias (MPAL), thus, ALAL are those that either fail to show evidence of either myeloid, B, or T-lymphoid lineages, or show evidence of commitment to more than one lineage, respectively. The so-called subgroup ALAL, not otherwise specified (NOS) is a catch-all category of diseases that express a combination of markers that do not allow their classification as either other ALAL, and in which a definitive classification along a single lineage is difficult. All those infrequent entities are considered as high-risk diseases and show a poor prognosis when treated with either conventional chemotherapy used for acute myeloid leukemia (AML) or acute lymphoblastic leukemia (ALL). More aggressive approaches such as the FLAG-IDA regimen (fludarabine, cytarabine, granulocyte colony-stimulating factor, and idarubicin) have been explored in patients with ALAL, and