Ambiguous lineage acute leukemia (ALAL) is a rare subtype of acute leukemia and is defined immunologically. ALAL consists of mixed phenotype acute leukemia (MPAL) and acute undifferentiated leukemia (AUL). MPAL is further divided into subtypes such as B/M MPAL, T/M MPAL, and B/T MPAL. Recently, the genetic basis of MPAL has been revealed as an acquisition of mutations in immature hematopoietic progenitors. There are shared genetic features between B/M MPAL with ZNF384 and B-cell acute lymphoblastic leukemia (ALL) with ZNF384 as well as T/M MPAL and early T-cell precursor ALL. Treatment for ALAL has not been established. However, treatment of ALL-type is significantly more effective than treatment of acute myelogenous leukemia. Generally, the prognosis of pediatric ALAL is worse than that of pediatric ALL. Treatment selection based on the genetic background is recommended. ALAL with genetic features of ALL, such as BCR-ABL or KMT2A alterations, and CD19 positive ALAL should be treated using ALL treatment. Treatment switching, either ALL-type to AML-type or vice versa, is beneficial for few ALAL cases. Hematopoietic stem cell transplantation is indicated for patients with poor efficacy of induction treatment.
This is a preview of subscription content, log in to check access.
Bene MC, Castoldi G, Knapp W, et al. Proposals for the immunological classification of acute leukemias. European Group for the Immunological Characterization of Leukemias (EGIL). Leukemia. 1995;9(10):1783–6.PubMedGoogle Scholar
Arber DA, Orazi A, Hasserijian R, et al. The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia. Blood. 2016;127(20):2391–405.CrossRefGoogle Scholar
Rossi JG, Bernasconi AR, Alonso CN, et al. Lineage switch in childhood acute leukemia: an unusual event with poor outcome. Am J Hematol. 2012;87(9):890–7.CrossRefGoogle Scholar
Hrusak O, de Haas V, Stancikova J, et al. International cooperative study identifies treatment strategy in childhood ambiguous lineage leukemia. Blood. 2018;132(3):264–76.CrossRefGoogle Scholar
Maruffi M, Sposto R, Oberley MJ, et al. Therapy for children and adults with mixed phenotype acute leukemia: a systematic review and meta-analysis. Leukemia. 2018;32(7):1515–28.CrossRefGoogle Scholar
Alexander TB, Gu Z, Iacobucci I, et al. The genetic basis and cell of origin of mixed phenotype acute leukaemia. Nature. 2018;562(7727):373–9.CrossRefGoogle Scholar
Mi X, Griffin G, Lee W, et al. Genomic and clinical characterization of B/T mixed phenotype acute leukemia reveals recurrent features and T-ALL like mutations. Am J Hematol. 2018;93(11):1358–67.CrossRefGoogle Scholar
Gerr H, Zimmermann M, Schrappe M, et al. Acute leukaemias of ambiguous lineage in children: characterization, prognosis and therapy recommendations. Br J Haematol. 2010;149(1):84–92.CrossRefGoogle Scholar
Matutes E, Pickl WF, Van't Veer M, et al. Mixed-phenotype acute leukemia: clinical and laboratory features and outcome in 100 patients defined according to the WHO 2008 classification. Blood. 2011;117(11):3163–71.CrossRefGoogle Scholar
Nakagawa S, Okamoto Y, Kodama Y, et al. Importance of acute lymphoblastic leukemia-type therapy for bilineal acute leukemia. J Pediatr Hematol Oncol. 2018;41(6):504–6. [Epub ahead of print]CrossRefGoogle Scholar
Tian H, Xu Y, Liu L, et al. Comparison of outcomes in mixed phenotype acute leukemia patients treated with chemotherapy and stem cell transplantation versus chemotherapy alone. Leuk Res. 2016;45:40–6.CrossRefGoogle Scholar