Evaluation at single cell level of residual Philadelphia negative hemopoietic stem cells in chronic phase CML patients

Citation
S. Akel et al., Evaluation at single cell level of residual Philadelphia negative hemopoietic stem cells in chronic phase CML patients, CANC GENET, 122(2), 2000, pp. 93-100
Citations number
40
Categorie Soggetti
Onconogenesis & Cancer Research
Journal title
CANCER GENETICS AND CYTOGENETICS
ISSN journal
01654608 → ACNP
Volume
122
Issue
2
Year of publication
2000
Pages
93 - 100
Database
ISI
SICI code
0165-4608(20001015)122:2<93:EASCLO>2.0.ZU;2-3
Abstract
In chronic myeloid leukemia, accurate determination of Ph- Hemopoietic stem cells (HSC) in peripheral blood (PB), bone marrow (BM) and leukapheresis p roducts is important for the selection of patients for whom mobilization, c ollection, and autografting of Ph- HSC are envisaged. To this effect, the B CR/ABL fusion was assessed at the single cell level in 25 sets of PB and BM samples using dual-color I-FISH in immunophenotyped CD34(+) cells and RT-P CR of individual CFU-GM colonies. In 15 cases found to be 100% Ph+, the res pective BCR/ABL gene was absent in 30% of CD34(+) cells, while the respecti ve transcripts could not be identified in 17% of CFU-GM. The mean percentag e of BCR/ABL(-) CD34(+) cells and CFU-GM cells was higher (38% and 29%, res pectively) in untreated patients than in treated patients (24% and 7%, resp ectively). In eight cases with cytogenetic response (CgR), the percentage o f Ph- metaphases correlated with the level of BCR/ABL(-) colonies in BM and PB and with the proportion of BCR/ABL(-) CD34(+) cells in the BM. Immunoph enotyping and FISH was fast, easy, always informative, and quantitative for the BCR/ABL- CD34(+) cells. Our results show that (a) at early diagnosis a high frequency of BCR/ABL(-) HSC circulate in the PB and that Ph- hematopo iesis is not completely suppressed: (b) although normal clonogenic cells de cline rapidly within a few months after diagnosis, appreciable numbers of n ormal CD34(+) cells survive in chronic phase, especially in patients with C gR. (C) 2000 Elsevier Science Inc. All rights reserved.