TY - JOUR
T1 - Quantitation of minimal residual disease in acute myelogenous leukemia and myelodysplastic syndromes in complete remission by molecular cytogenetics of progenitor cells
AU - Engel, H.
AU - Drach, J.
AU - Keyhani, A.
AU - Jiang, S.
AU - Van, N. T.
AU - Kimmel, M.
AU - Sanchez-Williams, G.
AU - Goodacre, A.
AU - Andreeff, M.
N1 - Funding Information:
This work was supported in part by grants from the National Cancer Institute (CA55164, CA16672 and CA57639). The authors thank WJ Pagel (MD Anderson Cancer Center, University of Texas) for critical reading of the manuscript and Dr HM Schueler (Department of Gynecology, Cytogenetic Section, University of Cologne) for her support in correcting the karyotype analyses according to ISCN (1995).
PY - 1999
Y1 - 1999
N2 - 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.
AB - 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.
KW - Acute myelogenous leukemia
KW - Cytogenetics
KW - Fluorescence activated cell sorting
KW - Fluorescence in situ hybridization
KW - Minimal residual disease
KW - Myelodysplastic syndrome
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U2 - 10.1038/sj.leu.2401359
DO - 10.1038/sj.leu.2401359
M3 - Article
C2 - 10214863
AN - SCOPUS:0032916077
SN - 0887-6924
VL - 13
SP - 568
EP - 577
JO - Leukemia
JF - Leukemia
IS - 4
ER -