PMID- 23851302 OWN - NLM STAT- MEDLINE DCOM- 20131217 LR - 20131021 IS - 1873-2399 (Electronic) IS - 0301-472X (Linking) VI - 41 IP - 10 DP - 2013 Oct TI - Genotypic and functional diversity of phenotypically defined primitive hematopoietic cells in patients with chronic myeloid leukemia. PG - 837-47 LID - S0301-472X(13)00628-0 [pii] LID - 10.1016/j.exphem.2013.07.001 [doi] AB - Much progress has been made in the management of chronic-phase chronic myeloid leukemia (CP-CML), but there is a continuing imperative to develop curative treatments, predict patient responses to specific modalities, and anticipate disease relapse or progression. These needs underlie continuing interest in methods to detect and quantify the relevant leukemic cells in clinical samples with improved reliability and specificity. We report the results of comparing three methods to enumerate primitive CP-CML cells in the same samples: genotyping CD34(+)38(-) cells directly by fluorescence in situ hybridization, and measuring BCR-ABL1 transcript-genotyped colony-forming cell outputs in either 5-week long-term cultures (LTCs) containing non-engineered mouse fibroblasts or in 6-week LTCs containing mouse fibroblasts engineered to produce human Steel factor, granulocyte colony-stimulating factor, and IL-3. The results demonstrate that the first two methods significantly overestimate the prevalence of primitive CP-CML cells by comparison to the third. In additional studies, we found that CML-CD34(+) cells can repopulate the marrow and spleen of serially transplanted adult NOD/SCID-IL-2Rgamma chain-null mice for more than 1 year with an almost exclusive myeloid differentiation in primary and secondary recipients and without evidence of disease progression. These findings underscore the importance of long-term functional in vitro and in vivo endpoints to identify and characterize CP-CML stem cells. CI - Crown Copyright (c) 2013. Published by Elsevier Inc. All rights reserved. FAU - Sloma, Ivan AU - Sloma I AD - Terry Fox Laboratory, British Columbia Cancer Agency, Vancouver, British Columbia, Canada; Laboratoire d'Hematologie, Hopital Paul Brousse, Assistance Publique des Hopitaux de Paris, Villejuif, France. FAU - Beer, Philip A AU - Beer PA FAU - Saw, Kyi Min AU - Saw KM FAU - Chan, Matthew AU - Chan M FAU - Leung, Donna AU - Leung D FAU - Raghuram, Kamini AU - Raghuram K FAU - Brimacombe, Cedric AU - Brimacombe C FAU - Johnston, Bobby AU - Johnston B FAU - Lambie, Karen AU - Lambie K FAU - Forrest, Donna AU - Forrest D FAU - Jiang, Xiaoyan AU - Jiang X FAU - Eaves, Connie J AU - Eaves CJ LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20130711 PL - Netherlands TA - Exp Hematol JT - Experimental hematology JID - 0402313 RN - EC 2.7.10.2 (Fusion Proteins, bcr-abl) SB - IM MH - Animals MH - Bone Marrow Cells/cytology MH - Bone Marrow Transplantation MH - Cells, Cultured MH - Female MH - Fusion Proteins, bcr-abl/genetics MH - Genes, abl/genetics MH - *Genetic Variation MH - Genotype MH - Hematopoietic Stem Cells/cytology/metabolism/*pathology MH - Humans MH - In Situ Hybridization MH - Leukemia, Myeloid, Chronic-Phase/*genetics/*pathology MH - Male MH - Mice MH - Mice, SCID MH - Phenotype MH - Time Factors EDAT- 2013/07/16 06:00 MHDA- 2013/12/18 06:00 CRDT- 2013/07/16 06:00 PHST- 2013/06/28 00:00 [received] PHST- 2013/07/05 00:00 [accepted] PHST- 2013/07/16 06:00 [entrez] PHST- 2013/07/16 06:00 [pubmed] PHST- 2013/12/18 06:00 [medline] AID - S0301-472X(13)00628-0 [pii] AID - 10.1016/j.exphem.2013.07.001 [doi] PST - ppublish SO - Exp Hematol. 2013 Oct;41(10):837-47. doi: 10.1016/j.exphem.2013.07.001. Epub 2013 Jul 11.