To the Editor:
Mixed-phenotype acute leukemia (MPAL) is a rare, heterogeneous group of leukemia that comprises admixture of myeloid and lymphoid blasts (bilineal) or a single blast population co-expressing lymphoid and myeloid markers (biphenotypic). The accurate diagnosis relies on the immunophenotype of flow cytometric or immunostaining findings.1-3 European Group of Immunological Characterization of Leukemia (EGIL) was released in 1990s to establish guidelines for the characterization of acute leukemia based on marker expression,2 and the World Health Organization (WHO) classification also acknowledges lineage-specific antibodies and genetic markers.2 In brief, the assignment of myeloid lineage depends on the expression of Myeloperoxidase (MPO); the assignment of monocytic differentiation depends on at least 2 of the following: Nonspecific Esterase, CD11c, CD14, CD64 or Lysosome; the assignment of B-lineage depends on CD19 and more than 1 or 2 strong expression of CD79a, cytoplasmic CD22 or CD10; the assignment of T-lineage depends on strong cytoplasmic CD3 (strong is equal to brighter than the normal T cells) or surface CD3 expression.1
Recent genetic studies reveal recurrent aberrations in MPAL, which have been integrated in the classification of MPAL with BCR::ABL1fusion, KMT2A rearrangement, ZNF384 rearrangement, andBCL11B rearrangement.1 Within these genetic aberrations, BCL11B rearrangement is particularly interesting. Inactivating mutations of BCL11B have been identified in up to 16% of T-acute lymphoblastic leukemia (T-ALL), indicating its likely role of tumor-suppressor gene for T-ALL.4,5 However, novel BCL11B rearrangements have been identified in MPAL, early T-precursor-ALL, and in poorly differentiated AML with aberrant T-cell antigen expression.6-10
The complex phenotype of MPAL creates not just a diagnostic challenge, but challenges in determining and initiating optimal therapy.11 Lack of prospective trials and varying classification systems leads to inability to define standard therapy. A recent retrospective study by an MPAL cohort from the Children’s Oncology Group (COG), suggests that ALL chemotherapy without HSCT may be the preferred initial therapy for pediatric MPAL.12Ongoing efforts are underway within COG to prospectively evaluate the use of high risk ALL therapy in MPAL. Here we report a diagnostically challenging T/My MPAL patient with BCL11B copy gain.