Abstract
Classification of acute leukemia is based on the commitment of leukemic cells to the myeloid or the lymphoid lineage. However, a small percentage of acute leukemia cases lack straightforward immunophenotypical lineage commitment. These leukemias of ambiguous lineage represent a heterogeneous category of acute leukemia that cannot be classified as either acute myeloid leukemia (AML) or acute lymphoid leukemia (ALL). The lack of clear classification of acute leukemias of ambiguous lineage as either AML or ALL is a hurdle in treatment choice for these patients. Here, we compared the microRNA (miRNA) expression profiles of 17 cases with acute leukemia of ambiguous lineage and 16 cases of AML, B-cell acute lymphoid leukemia (B-ALL), and T-cell acute lymphoid leukemia (T-ALL). We show that leukemias of ambiguous lineage do not segregate as a separate entity but exhibit miRNA expression profiles similar to AML, B-ALL, or T-ALL. We show that by using only 5 of the most lineage-discriminative miRNAs, we are able to define acute leukemia of ambiguous lineage as either AML or ALL. Our results indicate the presence of a myeloid or lymphoid lineage-specific genotype, as reflected by miRNA expression, in these acute leukemias despite their ambiguous immunophenotype. miRNA-based classification of acute leukemia of ambiguous lineage might be of additional value in therapeutic decision making.
Highlights
Acute leukemias are classified as myeloid or lymphoid by using immunologic markers that determine their lineage commitment
We show that leukemias of ambiguous lineage do not segregate as a separate entity but exhibit miRNA expression profiles similar to acute myeloid leukemia (AML), B-acute lymphoid leukemia (ALL), or T-cell acute lymphoid leukemia (T-ALL)
We show that by using only 5 of the most lineagediscriminative miRNAs, we are able to define acute leukemia of ambiguous lineage as either AML or ALL
Summary
Acute leukemias are classified as myeloid or lymphoid by using immunologic markers that determine their lineage commitment. Four percent of acute leukemia cases cannot be classified as acute myeloid leukemia (AML) or acute lymphoid leukemia (ALL) due to coexpression of both lymphoid and myeloid lineage markers [1,2,3,4,5,6]. The prognosis of leukemias of ambiguous lineage is worse compared with AML or ALL, and no specific treatment programs exist for these leukemias. To date, it is unsettled whether patients benefit from AML, ALL, or combination therapy, which might cause their mistreatment and poor prognosis [7,8,9,10,11,12]. The therapeutic strategies used for treatment of AML or ALL are considerably different, indicating the importance of Authors' Affiliations: Departments of 1Hematology and 2Epidemiology and Biostatistics, VU University Medical Center, Cancer Center Amsterdam, Amsterdam, the Netherlands
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