Detection of acute leukemia cells with mixed lineage leukemia (MLL) gene rearrangements by flow cytometry using monoclonal antibody 7.1.
Translocations involving 11q23 are among the most common genetic abnormalities in hematologic malignancies, occurring in approximately 5-10% of acute lymphoblastic leukemia (ALL) and 5% of acute myeloblastic leukemia (AML). In 11q23 translocations, the mixed lineage leukemia (MLL) gene on chromosome 11, band q23, is usually disrupted. The human homologue of the rat NG2 chondroitin sulfate proteoglycan molecule, as detected by the monoclonal antibody (moab) 7.1, was shown to be expressed on leukemic cells with MLL rearrangements of children with acute leukemia. We further investigated the reactivity of the moab 7.1 on 533 cell samples of adults (n = 215) and children (n = 318) with acute leukemias (271 AML, 217 B-lineage ALL, 37 T-lineage ALL, eight CD7+ CD56+ myeloid/natural killer cell precursor acute leukemias) by flow cytometry. In AML, 38 samples were positive for moab 7.1 ('20%-cut-off-level'). These moab 7.1-positive AML cases revealed a myelomonocytic-differentiated immunophenotype with coexpression of the NK cell marker CD56 in 33 of 38 cases. Two of eight cell samples of the recently described CD7+ CD56+ myeloid/natural killer cell precursor acute leukemia entity reacted with moab 7.1. In ALL, 35 samples mostly of the pro-B-ALL subtype (33 pro-B-ALL, one common-ALL, one pre-B-ALL) were positive for moab 7.1. 58 (81%) of 72 samples with MLL rearrangements were positive for moab 7.1 including 28/31 with a t(4;11), 16/17 with a t(9;11), 3/5 with a t(11;19), and 2/6 with a del(11)(q23). All moab 7.1-positive ALL (n = 34) and childhood AML (n = 17) cases revealed MLL rearrangements as detected by Southern blot analysis and RT-PCR. However, 11 adults with AML, and one adult with moab 7.1-positive CD7+ CD56+ myeloid/natural killer cell precursor acute leukemia were negative for MLL rearrangements as proved by Southern blot analysis. We conclude that moab 7.1 is a sensitive but not entirely specific marker for the identification of 11q23-associated AML and ALL by flow cytometry in children and adults.
Wuchter
C
C
Department of Hematology, Oncology and Tumor Immunology, Robert-Rössle Clinic, Charité, Humboldt-University Berlin, Germany.
Harbott
J
J
Schoch
C
C
Schnittger
S
S
Borkhardt
A
A
Karawajew
L
L
Ratei
R
R
Ruppert
V
V
Haferlach
T
T
Creutzig
U
U
Dörken
B
B
Ludwig
W D
WD
D000208:Acute Disease; D000328:Adult; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology*; D000912:Antibodies, Neoplasm / Q000276:immunology*; D000918:Antibody Specificity; D014408:Biomarkers, Tumor / Q000032:analysis / Q000235:genetics* / Q000276:immunology; D015139:Blotting, Southern; D002648:Child; D002880:Chromosomes, Human, Pair 11 / Q000235:genetics* / Q000648:ultrastructure; D004268:DNA-Binding Proteins / Q000032:analysis / Q000235:genetics* / Q000276:immunology; D005434:Flow Cytometry; D015321:Gene Rearrangement; D011495:Histone-Lysine N-Methyltransferase; D006801:Humans; D016130:Immunophenotyping; D007621:Karyotyping; D007938:Leukemia / Q000145:classification / Q000235:genetics / Q000473:pathology*; D051788:Myeloid-Lymphoid Leukemia Protein; D014411:Neoplastic Stem Cells / Q000737:chemistry* / Q000648:ultrastructure; D011237:Predictive Value of Tests; D011519:Proto-Oncogenes; D051381:Rats; D012680:Sensitivity and Specificity; D014157:Transcription Factors; D014178:Translocation, Genetic
D000911:Antibodies, Monoclonal; D000912:Antibodies, Neoplasm; D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; C497422:KMT2A protein, human; C497424:Mllt1 protein, rat; D014157:Transcription Factors; D051788:Myeloid-Lymphoid Leukemia Protein; D011495:Histone-Lysine N-Methyltransferase