Response to Imatinib mesylate in chronic myeloid leukemia patients with variant BCR-ABL fusion transcripts.
Chronic myeloid leukemia patients with different BCR-ABL transcripts might respond differently to Imatinib mesylate. This prompted us to study BCR-ABL transcripts in chronic myeloid leukemia (CML) patients and their correlation with response to Imatinib. Eighty-seven chronic phase CML patients (median age, 35 years; range, 13-62 years; M/F, 59:28) were included in this study; 57 patients had received interferon-alpha and/or hydroxyurea, and 30 were previously untreated. All patients received Imatinib mesylate (Gleevec) 400 mg daily. Complete hematological remission rate and major cytogenetic response (CGR) rates were 99% and 72%, respectively. B3a2 transcript was present in 53% of patients, b2a2 in 39%, and both transcripts in 8% of patients. Twenty of 34(59%) patients with b2a2 type achieved complete CGR compared to 15 of 53 (28%) patients with b3a2, p = 0.04. Among 24 patients with minor or no CGR, six (25%) had b2a2 compared to 18 (75%) b3a2 type, p = 0.04. Expression of BCR-ABL/ABL% was higher in b3a2 patients compared to b2a2, p = 0.120. Pre-treatment characteristics-mean spleen size (6.6 vs. 6.4 cm, p = 0.868), mean hemoglobin (G/dl; 12.0 vs. 11.8, p = 0.690), mean WBC count (83 x 10(9) vs. 77 x 10(9)/L, p = 0.923), and mean platelets counts (360x10(9) vs. 340 x 10(9)/L, p = 0.712)-were not significantly different in the b3a2 vs. b2a2 transcripts groups. Our preliminary findings suggest that CML patients with b2a2 BCR-ABL transcript might have higher CGRs to Imatinib mesylate (Gleevec).
Sharma
Pratibha
P
Department of Medical Oncology, Institute Rotary Cancer Hospital, All India Institute of Medical Sciences, Ansari Nagar, New Delhi 110029, India.
Kumar
Lalit
L
Mohanty
Sujata
S
Kochupillai
Vinod
V
D000293:Adolescent; D000328:Adult; D001549:Benzamides; D020732:Cytogenetic Analysis; D005260:Female; D016044:Fusion Proteins, bcr-abl / Q000235:genetics*; D014644:Genetic Variation; D006801:Humans; D000068877:Imatinib Mesylate; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy* / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D010597:Pharmacogenetics; D010879:Piperazines / Q000008:administration & dosage*; D011743:Pyrimidines / Q000008:administration & dosage*; D012333:RNA, Messenger / Q000235:genetics*; D012074:Remission Induction; D016896:Treatment Outcome; D055815:Young Adult
D001549:Benzamides; D010879:Piperazines; D011743:Pyrimidines; D012333:RNA, Messenger; D000068877:Imatinib Mesylate; D016044:Fusion Proteins, bcr-abl