Mixed-phenotype acute leukemia: state-of-the-art of the diagnosis, classification and treatment

Abstract

Mixed-phenotype acute leukemia (MPAL) is a heterogeneous group of hematopoietic malignancies in which blasts show markers of multiple developmental lineages and cannot be clearly classified as acute myeloid or lymphoblastic leukemias. Historically, various names and classifications were used for this rare entity accounting for 2-5% of all acute leukemias depending on the diagnostic criterias used. The currently valid classification of myeloid neoplasms and acute leukemia published by the World Health Organization (WHO) in 2016 refers to this group of diseases as MPAL. Because adverse cytogenetic abnormalities are frequently present, MPAL is generally considered a disease with a poor prognosis. Knowledge of its treatment is limited to retrospective analyses of small patient cohorts. So far, no treatment recommendations verified by prospective studies have been published. The reported data suggest that induction therapy for acute lymphoblastic leukemia followed by allogeneic hematopoietic cell transplantation is more effective than induction therapy for acute myeloid leukemia or consolidation chemotherapy. The establishment of cooperative groups and international registries based on the recent WHO criterias are required to ensure further progress in understanding and treatment of MPAL. This review summarizes current knowledge on the diagnosis, classification, prognosis and treatment of MPAL patients.

Simultaneous B and T cell acute lymphoblastic leukemias in zebrafish driven by transgenic MYC: implications for oncogenesis and lymphopoiesis

“…Specifically, we predicted that hlk cancers were “pure” T-ALL, whereas hMYC-1 contained some B cells but mostly T-ALL cells, and that hMYC-2 samples contained the highest percentage of B and/or B-ALL cells relative to T-ALL cells. Alternatively, leukemias can express aberrant markers 22 , and hMYC might de-differentiate ALL, obscuring cell identities. In either case, B cell genes were highest in hMYC-2 and detectable in hMYC-1 also, so we next sought to definitively identify the cellular composition of hMYC cancers.…”

Simultaneous B and T cell acute lymphoblastic leukemias in zebrafish driven by transgenic MYC: implications for oncogenesis and lymphopoiesis

“…We hypothesized that hMYC-1 and -2 cancers might contain different proportions of lymphocytes, with hlk being “pure” T-ALL, but hMYC ALL comprised of varying amounts of T-ALL, B-ALL, and/or B cells. Alternatively, leukemias can express aberrant markers (22), and hMYC might de-differentiate ALL, obscuring cell identities. In either case, B cell genes were high in hMYC-2 and detectable in hMYC-1 also, so we next sought to definitively identify the cellular composition of hMYC cancers.…”

A unique case of mixed phenotype acute leukemia with t(9;22)(q34.1;q11.2);BCR-ABL1 sarcoma with epitheliotropism mimicking intestinal T cell lymphoma

“…However, the risk of MPAL in a patient with prior history of radiation therapy is unknown. MPAL is a rare entity that makes up 2-5% of acute leukemias, incidence varying based on the diagnostic algorithm used [5,28,29]. The disease entities are known to occur in both adults and pediatric populations, with a slight male predominance [4,5,29].…”

“…MPAL is a rare entity that makes up 2-5% of acute leukemias, incidence varying based on the diagnostic algorithm used [5,28,29]. The disease entities are known to occur in both adults and pediatric populations, with a slight male predominance [4,5,29]. The high-risk genetics associated with multilineage expression confers a poor prognosis [5].…”