Detection of clonal CD34+19+ progenitors in bone marrow of BCL2-IgH-positive follicular lymphoma patients

Blood. 1995 Dec 15;86(12):4691-8.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antigens, CD19 / analysis*
  • Antigens, CD34 / analysis*
  • Base Sequence
  • Bone Marrow / pathology*
  • Bone Marrow Purging*
  • Bone Marrow Transplantation / adverse effects
  • Cell Separation
  • Clone Cells / pathology*
  • Female
  • Flow Cytometry
  • Humans
  • Immunoglobulin Heavy Chains / genetics*
  • Immunophenotyping
  • Lymphoma, Follicular / genetics
  • Lymphoma, Follicular / pathology*
  • Lymphoma, Follicular / therapy
  • Male
  • Middle Aged
  • Molecular Sequence Data
  • Neoplasm, Residual
  • Neoplastic Stem Cells / transplantation
  • Oncogene Proteins, Fusion / genetics*
  • Proto-Oncogene Proteins / genetics*
  • Proto-Oncogene Proteins c-bcl-2
  • Recurrence
  • Sensitivity and Specificity

Substances

  • Antigens, CD19
  • Antigens, CD34
  • Immunoglobulin Heavy Chains
  • Oncogene Proteins, Fusion
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-bcl-2