Minimal residual disease (MRD) in remission t(8;21) AML and in vivo differentiation detected by FISH and CD34+ cell sorting.
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 2/44,000 (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.
Varella-Garcia
M
M
Division of Medical Oncology, University of Colorado Health Sciences and Cancer Centers, Denver 80262, USA.
Hogan
C J
CJ
Odom
L F
LF
Murata-Collins
J L
JL
Ai
H
H
Chen
L
L
Richkind
K
K
Paskulin
G
G
Andreeff
M
M
Brizard
A
A
McGavran
L
L
Gemmill
R M
RM
Berger
R
R
Drabkin
H A
HA
D000208:Acute Disease; D018952:Antigens, CD34 / Q000032:analysis*; D002469:Cell Separation; D002891:Chromosomes, Human, Pair 21; D002898:Chromosomes, Human, Pair 8; D005189:False Positive Reactions; D005434:Flow Cytometry; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007621:Karyotyping; D007951:Leukemia, Myeloid / Q000235:genetics* / Q000473:pathology*; D018365:Neoplasm, Residual; D012074:Remission Induction; D014178:Translocation, Genetic
D018952:Antigens, CD34