Bcr-abl-positive and -negative clonogenic cells in CML patients undergoing long-term interferon treatment.
Bone marrow (BM) and peripheral blood cell (PBC) samples of 11 Philadelphia (Ph) chromosome-positive chronic myelogenous leukemia (CML) patients in long-lasting hematologic remission induced by interferon (IFN) treatment were examined for the presence of leukemic hematopoietic precursor cells. Southern blot analysis revealed residual leukemic cells in BM samples of four patients, whereas seven patients showed no aberrant bands. Reverse transcription polymerase chain reaction (RT-PCR), however, amplified bcr-abl-specific cDNA in unfractionated BM or PBC samples in all 11 patients. The patients demonstrating bcr rearrangements in Southern blots had either a mosaic pattern (three patients) of bcr-abl-negative and positive colony-forming precursors (CFU-GEMM, BFU-E, CFU-GM, CFU-Mega), or all colonies were derived from leukemic precursors (one patient). However, in soft agar cultures of four patients without aberrant bands in Southern blots, only colonies without amplifiable bcr-abl transcripts were detectable. In another patient, few bcr-abl-positive colonies were found after 44 months of treatment, but not after 53 and 56 months of therapy. In these patients, therefore, residual disease detectable by PCR analysis of unfractionated cell samples does not appear to reside in the colony-forming cell compartment. The prognostic implications of these observations and the nature of the remaining bcr-abl-positive cells within unfractionated cell samples remain to be determined.
Wandl
U B
UB
Department of Internal Medicine (Cancer Research), West German Cancer Center, University of Essen Medical School.
Bützler
R
R
Niederle
N
N
Kloke
O
O
Mengelkoch
B
B
Becher
R
R
Seeber
S
S
Opalka
B
B
D000328:Adult; D015139:Blotting, Southern; D001853:Bone Marrow / Q000473:pathology; D005260:Female; D016044:Fusion Proteins, bcr-abl / Q000235:genetics*; D006801:Humans; D007372:Interferons / Q000008:administration & dosage / Q000627:therapeutic use*; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000235:genetics* / Q000473:pathology / Q000628:therapy; D008297:Male; D008875:Middle Aged; D014411:Neoplastic Stem Cells / Q000737:chemistry* / Q000473:pathology; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000032:analysis; D012334:RNA, Neoplasm / Q000032:analysis; D012194:RNA-Directed DNA Polymerase; D012074:Remission Induction; D013997:Time Factors; D014407:Tumor Cells, Cultured / Q000737:chemistry / Q000473:pathology; D014410:Tumor Stem Cell Assay
D012333:RNA, Messenger; D012334:RNA, Neoplasm; D007372:Interferons; D016044:Fusion Proteins, bcr-abl; D012194:RNA-Directed DNA Polymerase