Detection of clonal CD34+19+ progenitors in bone marrow of BCL2-IgH-positive follicular lymphoma patients.
The frequent occurrence of BCL2-IgH rearrangements in follicular lymphoma (FL) makes detection of low numbers of tumor cells possible by polymerase chain reaction (PCR). The presence of BCL2-IgH in the bone marrow (BM) and peripheral blood of many FL patients at the time of autografting has led to the suggestion that selection of the CD34-enriched fraction may lead to reinfusion of lower numbers of tumor cells. To address this issue, we PCR-amplified BCL2-IgH from fluorescence-activated cell sorting (FACS)-purified BM CD34+ and CD34- fractions in seven FL patients showing a PCR-detectable translocation in the major breakpoint region of BCL2, five of which showed morphological BM involvement. The total CD34+ fraction showed diminished but residual positivity in the first two cases tested. Therefore, BM cells from the remaining five patients were sorted for the CD34+19- immature population, the CD34+19+ B-cell precursors, and the CD34-19+ mature B-cell fraction. The CD34+19- subpopulation was negative in four of five, despite evident BM infiltration in three cases. In contrast, the CD34+19+ fraction was positive in all three cases tested. These cells represented 0% to 50% (mean, 18%) of the total CD34+ population, suggesting that, if reinfusion of BCL2-IgH-positive cells plays a role in postautograft relapse in FL, therapeutic CD34 selection procedures should include additional purging of the CD34+19+ B-cell precursors or, at least, assessment of the proportion of CD19+ cells in the CD34+ fraction and its correlation with clinical outcome postreinfusion.
Macintyre
E A
EA
Department of Laboratory and Clinical Hematology, CNRS URA 1461, Hôpital Necker Enfants-Malades, Paris, France.
Belanger
C
C
Debert
C
C
Canioni
D
D
Turhan
A G
AG
Azagury
M
M
Hermine
O
O
Varet
B
B
Flandrin
G
G
Schmitt
C
C
D000328:Adult; D018941:Antigens, CD19 / Q000032:analysis*; D018952:Antigens, CD34 / Q000032:analysis*; D001483:Base Sequence; D001853:Bone Marrow / Q000473:pathology*; D016465:Bone Marrow Purging; D016026:Bone Marrow Transplantation / Q000009:adverse effects; D002469:Cell Separation; D002999:Clone Cells / Q000473:pathology*; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000235:genetics*; D016130:Immunophenotyping; D008224:Lymphoma, Follicular / Q000235:genetics / Q000473:pathology* / Q000628:therapy; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D018365:Neoplasm, Residual; D014411:Neoplastic Stem Cells / Q000637:transplantation; D015514:Oncogene Proteins, Fusion / Q000235:genetics*; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D019253:Proto-Oncogene Proteins c-bcl-2; D012008:Recurrence; D012680:Sensitivity and Specificity
D018941:Antigens, CD19; D018952:Antigens, CD34; D007143:Immunoglobulin Heavy Chains; D015514:Oncogene Proteins, Fusion; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2