title: MicroRNA profiling can classify acute leukemias of ambiguous lineage as either acute myeloid leukemia or acute lymphoid leukemia.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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).
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors: Department of Hematology, VU University Medical Center, Cancer Center Amsterdam, Amsterdam, The Netherlands.
authors: David C
authors: DC
authors: de Leeuw
authors: Willemijn
authors: W
authors: van den Ancker
authors: Fedor
authors: F
authors: Denkers
authors: Renée X
authors: RX
authors: de Menezes
authors: Theresia M
authors: TM
authors: Westers
authors: Gert J
authors: GJ
authors: Ossenkoppele
authors: Arjan A
authors: AA
authors: van de Loosdrecht
authors: Linda
authors: L
authors: Smit
mesh_terms: D000208:Acute Disease; D015703:Antigens, CD / Q000378:metabolism; D045744:Cell Line, Tumor; D016000:Cluster Analysis; D005434:Flow Cytometry; D020869:Gene Expression Profiling; D015973:Gene Expression Regulation, Leukemic; D018922:HL-60 Cells; D006801:Humans; D016130:Immunophenotyping; D007938:Leukemia / Q000145:classification / Q000235:genetics* / Q000378:metabolism; D007951:Leukemia, Myeloid / Q000175:diagnosis / Q000235:genetics / Q000378:metabolism; D035683:MicroRNAs / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis; D015452:Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / Q000175:diagnosis / Q000235:genetics / Q000378:metabolism; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000175:diagnosis / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D015703:Antigens, CD; D035683:MicroRNAs; C525709:MIR221, human; C525067:MIR223, human; C552430:MIRN23a microRNA, human; C531388:MIRN27 microRNA, human; C531408:mirn199 microRNA, human