Faculty Collaboration Database

Persistence of dormant leukemic progenitors during interferon-induced remission in chronic myelogenous leukemia. Analysis by polymerase chain reaction of individual colonies. J Clin Invest 1994 Oct;94(4):1383-9

Date

10/01/1994

Pubmed ID

7929813

Pubmed Central ID

PMC295262

DOI

10.1172/JCI117473

Scopus ID

2-s2.0-0028018343 (requires institutional sign-in at Scopus site)   98 Citations

Abstract

Interferon-alpha induces durable cytogenetic remissions in about one-quarter of newly diagnosed patients with chronic myelogenous leukemia (CML). Even so, after short-term follow-up, previous studies have shown that residual leukemic cells can be detected by the polymerase chain reaction (PCR) in all of these individuals. The objectives of our study were therefore to obtain long-term follow-up data on residual disease in a cohort of complete responders and to determine if leukemic cells with clonogenic potential are present in patients despite the absence of relapse. We performed (a) serial analysis of blood and/or bone marrow for a reverse transcriptase PCR amplified BCR-ABL transcript at times well beyond the point that cytogenetic remission was first attained and (b) reverse transcriptase PCR of individually plucked myeloid and erythroid colonies for the presence of the same transcript. Seven CML patients who had previously attained complete cytogenetic remission while on interferon-alpha were investigated. Six of the seven patients were in complete cytogenetic remission at the time of analysis, whereas one patient had early evidence of cytogenetic relapse. With ongoing therapy, five patients with the longest follow-up eventually achieved PCR negativity at time periods of 27, 32, 36, 49, and 67 mo after a complete cytogenetic remission was first noted. Even so, residual disease was detected in progenitor cells derived from two patients, each of whom had been in continuous cytogenetic remission for approximately 2.5 and 3.5 yr, respectively. Progenitors expressing BCR-ABL transcripts were also detected in the patient with early cytogenetic relapse. These observations demonstrate that residual disease resides in colony-forming cells that should have the potential to repopulate the bone marrow. However, the presence of a minority of Ph-positive CML progenitor cells for a very long period of time is still compatible with durable remission, confirming that a situation of tumor dormancy may be induced in CML by interferon therapy.

Author List

Talpaz M, Estrov Z, Kantarjian H, Ku S, Foteh A, Kurzrock R

Author

Razelle Kurzrock MD Center Associate Director, Professor in the Medicine department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Adult
Base Sequence
Bone Marrow
Cohort Studies
Follow-Up Studies
Humans
Interferon-alpha
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Male
Middle Aged
Molecular Sequence Data
Nucleic Acid Hybridization
Oncogene Proteins
Philadelphia Chromosome
Polymerase Chain Reaction
Protein-Tyrosine Kinases
Proto-Oncogene Proteins
Proto-Oncogene Proteins c-bcr
RNA, Messenger
Remission Induction
Stem Cells
Transcription, Genetic
Tumor Cells, Cultured