title: Benign marrow progenitors are enriched in the CD34+/HLA-DRlo population but not in the CD34+/CD38lo population in chronic myeloid leukemia: an analysis using interphase fluorescence in situ hybridization.
abstract: Fluorescence in situ hybridization (FISH) was used to discriminate between benign and malignant cells in sorted populations of chronic myelogenous leukemia (CML) marrow. FISH has the advantage of allowing for a cell by cell analysis of the breakpoint cluster region (BCR) gene rearrangement immediately after flow sorting in nondividing G0/G1 cells that are potentially transcriptionally inactive. We initially selected CD34+ cells with very low expression of the activation antigen CD38 as a candidate phenotype for an immature and hypothetically more benign cell population, but found no enrichment for Ph negativity in that subtype. In five CML samples, 55% +/- 3.3% (mean +/- SE) of CD34+/CD38hi cells had the BCR gene rearrangement, similar to 57% +/- 3.7% seen in the CD34+/CD38lo population. In contrast, subsequent experiments (n = 4) determined that the CD34+/HLA-DRlo population in CML marrow does contain an increased proportion of benign cells: 15% +/- 1% of the CD34+/DRlo cells were BCR rearranged, compared with 52% +/- 5.8% of the CD34+/DRhi cells (P = .001). Our results indicate that benign progenitors in CML are enriched within the CD34+ cells with low DR antigen expression, but not low CD38 expression. One possible interpretation of these observations is that low CD38 antigen expression is not as useful as low HLA-DR expression for isolating immature cells.
authors.affiliation: Fred Hutchinson Cancer Research Center, Seattle, WA 98104-2092, USA.
authors.forename: J A
authors.initials: JA
authors.lastname: Kirk
authors.forename: J A
authors.initials: JA
authors.lastname: Reems
authors.forename: B A
authors.initials: BA
authors.lastname: Roecklein
authors.forename: D R
authors.initials: DR
authors.lastname: Van Devanter
authors.forename: E M
authors.initials: EM
authors.lastname: Bryant
authors.forename: J
authors.initials: J
authors.lastname: Radich
authors.forename: S
authors.initials: S
authors.lastname: Edmands
authors.forename: A
authors.initials: A
authors.lastname: Lee
authors.forename: B
authors.initials: B
authors.lastname: Torok-Storb
mesh_terms: D036541:ADP-ribosyl Cyclase; D051997:ADP-ribosyl Cyclase 1; D000328:Adult; D015703:Antigens, CD / Q000032:analysis*; D018952:Antigens, CD34; D000943:Antigens, Differentiation / Q000032:analysis*; D001853:Bone Marrow / Q000473:pathology*; D005260:Female; D016044:Fusion Proteins, bcr-abl / Q000235:genetics*; D015321:Gene Rearrangement; D006684:HLA-DR Antigens / Q000032:analysis*; D006412:Hematopoietic Stem Cells / Q000473:pathology*; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007399:Interphase; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000235:genetics / Q000473:pathology*; D008297:Male; D008562:Membrane Glycoproteins; D008875:Middle Aged; D009699:N-Glycosyl Hydrolases / Q000032:analysis*
chemical_list: D015703:Antigens, CD; D018952:Antigens, CD34; D000943:Antigens, Differentiation; D006684:HLA-DR Antigens; D008562:Membrane Glycoproteins; D016044:Fusion Proteins, bcr-abl; D009699:N-Glycosyl Hydrolases; D036541:ADP-ribosyl Cyclase; C498154:CD38 protein, human; D051997:ADP-ribosyl Cyclase 1