Most cases of acute leukemia can be assigned to myeloid, B, or T lineage according to morphologic features and immunophenotype. However, 3% to 5% of all cases of acute leukemias in adults constitute a heterogeneous subset that cannot be definitively assigned to a certain cell lineage.1 These entities have been referred to as acute leukemias of ambiguous lineage (ALALs). Acute undifferentiated leukemia (AUL) has been categorized by WHO as a rare subtype of ALAL2 that expresses no known lineage-specific markers but instead may express only HLA-DR, CD34, and/or CD38, and may be positive for terminal deoxynucleotidyl transferase (TdT).3 The overall prognosis of AUL is poor, and because of its low incidence, knowledge about AUL is limited in terms of clinical and biological characteristics. No standard treatment approach exists for patients with AUL.
Heesch S, Neumann M, Schwartz S, . Acute leukemias of ambiguous lineage in adults: molecular and clinical characterization. Ann Hematol 2013;92:747–758.
Arber DA, Orazi A, Hasserjian R, . The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia. Blood 2016;127:2391–2405.
Kurosawa S, Toya T, Kishida Y, . Outcome of patients with acute undifferentiated leukemia after allogeneic hematopoietic stem cell transplantation. Leuk Lymphoma 2018;59:3006–3009.
Comont T, Tavitian S, Bardiaux L, . Platelet transfusion refractoriness in patients with acute myeloid leukemia treated by intensive chemotherapy. Leuk Res 2017;61:62–67.
Lao ZT, Ding LW, An O, . Mutational and transcriptomic profiling of acute leukemia of ambiguous lineage reveals obscure but clinically important lineage bias. Haematologica 2019;104:e200–203.
Brito-Babapulle F, Pullon H, Layton DM, . Clinicopathological features of acute undifferentiated leukaemia with a stem cell phenotype. Br J Haematol 1990;76:210–214.
Cuneo A, Ferrant A, Michaux JL, . Cytogenetic and clinicobiological features of acute leukemia with stem cell phenotype: study of nine cases. Cancer Genet Cytogenet 1996;92:31–36.
Liu QF, Fan ZP, Wu MQ, . Allo-HSCT for acute leukemia of ambiguous lineage in adults: the comparison between standard conditioning and intensified conditioning regimens. Ann Hematol 2013;92:679–687.
Guru Murthy GS, Dhakal I, Lee JY, . Acute leukemia of ambiguous lineage in elderly patients—analysis of survival using Surveillance Epidemiology and End Results-Medicare database. Clin Lymphoma Myeloma Leuk 2017;17:100–107.
Dang L, Su SM. Isocitrate dehydrogenase mutation and (R)-2-hydroxyglutarate: from basic discovery to therapeutics development. Annu Rev Biochem 2017;86:305–331.
Marcucci G, Maharry K, Wu YZ, . IDH1 and IDH2 gene mutations identify novel molecular subsets within de novo cytogenetically normal acute myeloid leukemia: a Cancer and Leukemia Group B study. J Clin Oncol 2010;28:2348–2355.
Guo JU, Su Y, Zhong C, . Emerging roles of TET proteins and 5-hydroxymethylcytosines in active DNA demethylation and beyond. Cell Cycle 2011;10:2662–2668.
DiNardo CD, Stein EM, de Botton S, . Durable remissions with ivosidenib in IDH1-mutated relapsed or refractory AML. N Engl J Med 2018;378:2386–2398.
Norsworthy KJ, Luo L, Hsu V, . FDA approval summary: ivosidenib for relapsed or refractory acute myeloid leukemia with an isocitrate dehydrogenase-1 mutation. Clin Cancer Res 2019;25:3205–3209.
Ivosidenib [package insert]. Cambridge, MA: Agios Pharmaceuticals, Inc; 2019.