Fluorescence in situ hybridization monitoring of BCR-ABL-positive neutrophils in chronic-phase chronic myeloid leukemia patients during the primary stage of imatinib mesylate therapy.
We describe a method for monitoring chronic myeloid leukemia (CML) patients treated with imatinib that uses fluorescence in situ hybridization (FISH) to detect BCR-ABL in peripheral blood (PB) granulocytes. First, we compared this method, termed Neutrophil-FISH, with interphase FISH (i-FISH) analysis of bone marrow (BM), i-FISH analysis of PB mononuclear cells, and conventional cytogenetic analysis (CCA) of BM in 30 consecutive CML patients. We found the percentage of BCR-ABL-positive neutrophils as determined by Neutrophil-FISH to correlate best with the percentage of Philadelphia chromosome-positive metaphases in the BM determined by CCA (y = 0.8818x + 5.7249; r(2) = 0.968). We then performed a serial Neutrophil-FISH study of 10 chronic-phase CML patients treated with imatinib and found that the technique could clearly separate imatinib responders from nonresponders within 12 weeks of drug administration. There was a significant difference in the percentages of BCR-ABL-positive neutrophils between responder (mean 3 SD, 18.2% 3 11.8%) and nonresponder (82.4% 3 5.1%) groups at 12 weeks (P < .0001, Student t test).Together with real-time quantitative polymerase chain reaction analysis, Neutrophil-FISH represents another useful method for monitoring CML patients during the primary myelosuppressive stage of imatinib therapy because it is a quick, simple, and reliable method for assessing cytogenetic response.
Takahashi
Naoto
N
University of Saskatchewan, College of Medicine, Pathology Department and Saskatchewan Cancer Centre, Saskatoon, Canada.
Miura
Ikuo
I
Kobayashi
Yoshimi
Y
Kume
Masaaki
M
Yoshioka
Tomoko
T
Otane
Wataru
W
Ohtsubo
Kaori
K
Takahashi
Kaoru
K
Kitabayashi
Atsushi
A
Kawabata
Yoshinari
Y
Hirokawa
Makoto
M
Nishijima
Hirokazu
H
Ichinohasama
Ryo
R
Decoteau
John
J
Miura
Akira B
AB
Sawada
Ken-Ichi
K
D000970:Antineoplastic Agents / Q000008:administration & dosage*; D001549:Benzamides; D005260:Female; D016044:Fusion Proteins, bcr-abl / Q000096:biosynthesis*; D006801:Humans; D000068877:Imatinib Mesylate; D017403:In Situ Hybridization / Q000379:methods; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology; D015466:Leukemia, Myeloid, Chronic-Phase / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology*; D008297:Male; D008991:Monitoring, Physiologic / Q000379:methods; D009504:Neutrophils / Q000378:metabolism* / Q000473:pathology; D010879:Piperazines / Q000008:administration & dosage*; D011743:Pyrimidines / Q000008:administration & dosage*
D000970:Antineoplastic Agents; D001549:Benzamides; D010879:Piperazines; D011743:Pyrimidines; D000068877:Imatinib Mesylate; D016044:Fusion Proteins, bcr-abl