TY - JOUR
T1 - Minimal residual disease (MRD) in remission t(8;21) AML and in vivo differentiation detected by FISH and CD34+ cell sorting
AU - Varella-Garcia, M.
AU - Hogan, C. J.
AU - Odom, L. F.
AU - Murata-Collins, J. L.
AU - Ai, H.
AU - Chen, L.
AU - Richkind, K.
AU - Paskulin, G.
AU - Andreeff, M.
AU - Brizard, A.
AU - Mcgavran, L.
AU - Gemmill, R. M.
AU - Berger, R.
AU - Drabkin, H. A.
N1 - Funding Information:
We wish to acknowledge the assistance of the Flow Cytometry and Cytogenetics Cores of the University of Colorado Cancer Center. M Andreeff was supported by NIH PO1 CA 55164.
PY - 2001
Y1 - 2001
N2 - Many patients with t(8;21) AML have residual positive cells during remission. We previously developed D-FISH probes that detect both derivative chromosomes and the normal alleles. In negative controls, only 2/44000 (0.0045%) positive signals were observed. To investigate MRD, we examined specimens from 29 patients who had initially obtained CR. In remission patients, 61% had 1-4/2000 positive cells (0.05-0.19%). Higher frequencies were found in two patients in early relapse and in one patient in early remission. However, a negative test did not exclude relapse. Since false positives were negligible and because most t(8;21) AMLs express CD34, we asked whether cell sorting combined with FISH would increase the sensitivity. In one patient, we observed that 80% of CD34+ cells were t(8;21)+ at 2 months from initial clinical and cytogenetic remission. However, by 5 months the pre- and post-sorted populations contained 0.15% and 0.06% t(8;21) cells, respectively. Whereas essentially all t(8;21) cells in the initial specimen expressed CD34, only 0.6% were subsequently CD34+. These results are consistent with in vitro assays showing that residual t(8;21) cells undergo differentiation. Thus, FISH can identify MRD in a majority of t(8;21) patients and, combined with CD34+ selection, may provide an indirect assessment of the differentiation state of residual t(8;21) cells.
AB - Many patients with t(8;21) AML have residual positive cells during remission. We previously developed D-FISH probes that detect both derivative chromosomes and the normal alleles. In negative controls, only 2/44000 (0.0045%) positive signals were observed. To investigate MRD, we examined specimens from 29 patients who had initially obtained CR. In remission patients, 61% had 1-4/2000 positive cells (0.05-0.19%). Higher frequencies were found in two patients in early relapse and in one patient in early remission. However, a negative test did not exclude relapse. Since false positives were negligible and because most t(8;21) AMLs express CD34, we asked whether cell sorting combined with FISH would increase the sensitivity. In one patient, we observed that 80% of CD34+ cells were t(8;21)+ at 2 months from initial clinical and cytogenetic remission. However, by 5 months the pre- and post-sorted populations contained 0.15% and 0.06% t(8;21) cells, respectively. Whereas essentially all t(8;21) cells in the initial specimen expressed CD34, only 0.6% were subsequently CD34+. These results are consistent with in vitro assays showing that residual t(8;21) cells undergo differentiation. Thus, FISH can identify MRD in a majority of t(8;21) patients and, combined with CD34+ selection, may provide an indirect assessment of the differentiation state of residual t(8;21) cells.
KW - AML1
KW - Acute myeloid leukemia
KW - Chromosome translocation
KW - ETO
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U2 - 10.1038/sj.leu.2402219
DO - 10.1038/sj.leu.2402219
M3 - Article
C2 - 11516101
AN - SCOPUS:17944371518
SN - 0887-6924
VL - 15
SP - 1408
EP - 1414
JO - Leukemia
JF - Leukemia
IS - 9
ER -