Quantitation of minimal residual disease in acute myelogenous leukemia and myelodysplastic syndromes in complete remission by molecular cytogenetics of progenitor cells.
Detection of karyotypic clonal abnormalities are prognostically useful in patients with acute myelogenous leukemia (AML) and myelodysplastic syndromes (MDS), but cytogenetic methods are not sensitive enough to detect low numbers of residual leukemic cells in patients who have achieved complete remission (CR). Fluorescence in situ hybridization (FISH) and fluorescence activated cell sorting (FACS) were used to investigate the frequency and presence of minimal residual disease (MRD) in AML and MDS patients (n = 28) with monosomy of chromosomes 7, 17 and 18 and trisomy of chromosomes 6, 8, 9 and 10 in CR. MRD was detected in all patients with monosomy 7 (n = 10) and followed by relapse in eight patients after 4.8 +/- 3.1 months. In contrast, persistent leukemic cells occurred in 11/12 patients with trisomy 8, but only three of them relapsed after 7.7 +/- 4.0 months. Cox regression analysis showed that cytogenetic class and levels of clonal cells at CR were related to time to relapse (P = 0.001). The level of MRD identified patients at high and low risk of relapse. High absolute levels of proliferating residual leukemic cells correlated with monosomy 7 and high risk of relapse.
Engel
H
H
Department of Hematology, The University of Texas MD Anderson Cancer Center, Houston, USA.
Drach
J
J
Keyhani
A
A
Jiang
S
S
Van
N T
NT
Kimmel
M
M
Sanchez-Williams
G
G
Goodacre
A
A
Andreeff
M
M
D000208:Acute Disease; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000754:Anemia, Refractory, with Excess of Blasts / Q000175:diagnosis / Q000235:genetics / Q000473:pathology; D000943:Antigens, Differentiation / Q000032:analysis; D000951:Antigens, Neoplasm / Q000032:analysis; D002455:Cell Division; D002869:Chromosome Aberrations; D002897:Chromosomes, Human, Pair 7; D002999:Clone Cells / Q000737:chemistry / Q000648:ultrastructure; D018450:Disease Progression; D018572:Disease-Free Survival; D005260:Female; D005434:Flow Cytometry; D006412:Hematopoietic Stem Cells / Q000737:chemistry / Q000648:ultrastructure*; D006801:Humans; D016130:Immunophenotyping; D017404:In Situ Hybridization, Fluorescence; D007621:Karyotyping; D007951:Leukemia, Myeloid / Q000145:classification / Q000175:diagnosis / Q000235:genetics / Q000473:pathology*; D015993:Life Tables; D008297:Male; D008875:Middle Aged; D009006:Monosomy; D009190:Myelodysplastic Syndromes / Q000145:classification / Q000175:diagnosis / Q000235:genetics / Q000473:pathology*; D018365:Neoplasm, Residual; D014411:Neoplastic Stem Cells / Q000737:chemistry / Q000648:ultrastructure*; D016016:Proportional Hazards Models; D012008:Recurrence
D000943:Antigens, Differentiation; D000951:Antigens, Neoplasm