Heterogeneity in detecting Abl kinase mutations and better sensitivity using circulating plasma RNA.
Most studies test for mutations in the kinase domain of the abl gene in chronic myeloid leukemia (CML) using peripheral blood (PB) cells. Frequently, progression of the disease manifests with increased blasts in bone marrow (BM) and not in PB. Simultaneous analysis of plasma, PB cells and BM cells from 41 imatinib-resistant CML patients showed mutations in 63% of PB cells and 68% of plasma or BM cells (P = 0.04). In discordant patients, 13 mutations were detected in plasma, 11 in BM cells and 9 in PB cells. The T315I mutation was detected in plasma and BM but not PB cells in one patient. We detected no mutations in the plasma of 45 previously untreated CML patients, but two of these patients showed mutations in plasma and not cells by 9 months on therapy. Circulating plasma mRNA is a reliable alternative to BM mRNA for detecting ABL mutations.
Ma
W
W
Department of Hematology, Nichols Institute, Quest Diagnostics, San Juan Capistrano, CA 92690-6130, USA.
Kantarjian
H
H
Jilani
I
I
Gorre
M
M
Bhalla
K
K
Ottmann
O
O
Giles
F
F
Albitar
M
M
D000970:Antineoplastic Agents / Q000627:therapeutic use; D001549:Benzamides; D016903:Drug Monitoring / Q000379:methods; D019008:Drug Resistance, Neoplasm; D016044:Fusion Proteins, bcr-abl / Q000235:genetics*; D018740:Genetic Heterogeneity; D005820:Genetic Testing / Q000379:methods* / Q000592:standards; D006801:Humans; D000068877:Imatinib Mesylate; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000097:blood* / Q000188:drug therapy / Q000235:genetics*; D009154:Mutation; D010879:Piperazines / Q000627:therapeutic use; D010949:Plasma; D011743:Pyrimidines / Q000627:therapeutic use; D012333:RNA, Messenger / Q000097:blood* / Q000302:isolation & purification; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity
D000970:Antineoplastic Agents; D001549:Benzamides; D010879:Piperazines; D011743:Pyrimidines; D012333:RNA, Messenger; D000068877:Imatinib Mesylate; D016044:Fusion Proteins, bcr-abl