Detection of dormant chronic myeloid leukemia clones in the bone marrow of patients in complete molecular remission.
BACKGROUND
Several methods are available to detect MRD in patients with CML in complete molecular remission (CMR) and taking tyrosine kinase inhibitor (TKI) therapy.


METHODS
We performed clonogenic assays on mononuclear bone marrow cells from 14 patients. Of the 10 assessable samples, 6 were from patients in CMR and 4 from patients in complete cytogenetic remission but had detectable MRD using polymerase chain reaction (PCR) analysis (positive controls). At least 10 colonies per sample were microaspirated and individual colonies were subjected to PCR analysis.


RESULTS
Of the 6 patients in CMR, 5 harbored breakpoint cluster region abelson (BCR-ABL1) negative colonies but in 1 sample, 1 of the 10 colonies analyzed was positive for BCR-ABL1. Of the 4 patients with evidence of MRD in peripheral blood, 2 had negative and 2 had positive BCR-ABL1 colonies.


CONCLUSIONS
MRD is still detectable using clonogenic assays in some patients with CML after achieving CMR using TKI therapy, which is likely responsible for relapse on TKI discontinuation. Because of the large number of single colonies that need to be analyzed, the use of clonogenic assays in clinical practice to determine the feasibility of TKI discontinuation is not recommended.
Department of Leukemia, The University of Texas M.D. Anderson Cancer Center, Houston, TX. Electronic address: aquintas@mdanderson.org.
Alfonso
A
Quintás-Cardama
Srdana
S
Grgurevic
Uri
U
Rozovski
Ping
P
Li
Zeev
Z
Estrov
Jorge
J
Cortes
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001853:Bone Marrow / Q000378:metabolism / Q000473:pathology*; D045744:Cell Line, Tumor; D016044:Fusion Proteins, bcr-abl / Q000235:genetics; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy / Q000235:genetics / Q000473:pathology*; D008875:Middle Aged; D018365:Neoplasm, Residual / Q000175:diagnosis*; D012074:Remission Induction; D014410:Tumor Stem Cell Assay
C581634:BCR-ABL1 fusion protein, human; D016044:Fusion Proteins, bcr-abl
BCR-ABL1; Clonogenic assay; Colony; Minimal residual disease; Tyrosine kinase inhibitor