title: Molecular status of individual CFU-GM colonies derived from chemotherapy-mobilised peripheral blood stem cells in chronic myeloid leukaemia.
abstract: Following chemotherapy in chronic myeloid leukaemia (CML), some peripheral blood (PB) cells may be Philadelphia (Ph) chromosome negative. The BCR-ABL mRNA status of residual Ph+ progenitors is not known. We examined the BCR-ABL mRNA status of individual colony-forming-unit granulocyte-macrophage (CFU-GM) colonies derived from PB harvested following chemotherapy. Seven patients were treated with 200 mg/m2/day cytarabine and 20 mg/m2/day Idarubicin and followed by Lenograstim. PB collections commenced daily when the white blood cell count reached 0.6 x 10(9)/l and continued until at least 5 x 10(8)/kg nucleated cells were obtained. CD34+ cells, Ph status, and CFU-GM were estimated at each harvest. For each patient, up to 24 individual CFU-GM colonies were analysed for BCR-ABL status. Two cases were BCR-ABL negative on all colonies and completely Ph-, and another case was BCR-ABL positive in all colonies and completely Ph+. In contrast, in two patients all colonies were BCR-ABL negative, despite virtually complete Ph+ metaphases. The final assessible case had five of nine BCR-ABL negative colonies, despite 94% Ph+ metaphases. After chemotherapy priming, the PB may contain Ph+ CFU-GM that do not express BCR-ABL.
authors.affiliation: University Department of Haematology, Royal Liverpool University Hospital, United Kingdom.
authors.forename: C M
authors.initials: CM
authors.lastname: Broughton
authors.forename: P
authors.initials: P
authors.lastname: Sherrington
authors.forename: N T
authors.initials: NT
authors.lastname: Pender
authors.forename: R E
authors.initials: RE
authors.lastname: Clark
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D016044:Fusion Proteins, bcr-abl / Q000235:genetics*; D006098:Granulocytes / Q000187:drug effects; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy* / Q000235:genetics / Q000276:immunology*; D054438:Leukemia, Myeloid, Chronic, Atypical, BCR-ABL Negative / Q000188:drug therapy / Q000235:genetics / Q000276:immunology; D008264:Macrophages / Q000187:drug effects; D010677:Philadelphia Chromosome; D012333:RNA, Messenger / Q000032:analysis; D013234:Stem Cells / Q000187:drug effects*; D014182:Transplantation, Autologous; D016896:Treatment Outcome
chemical_list: D012333:RNA, Messenger; D016044:Fusion Proteins, bcr-abl