title: Prognostic importance of additional cytogenetic anomalies in chronic myeloid leukemia.
abstract: Additional chromosomal abnormalities (ACAs) in Philadelphia chromosome (Ph)-positive chronic myeloid leukemia (CML) are strongly associated with disease progression, but their prognostic impact and effect on treatment response are not clear. While the onset of ACAs in Ph-negative cells during treatment has been described, their origin and clinical significance remain to be clarified. Between January 2008 and January 2011, 105 patients with Ph-positive CML were analyzed. With a median follow-up of 25.5 months, 18 CML patients (17 %) with ACAs in either CP (n = 12) or advanced phases (n = 6) were identified. The median age of the patients was 53.5 years at diagnosis. ACAs were determined in Ph-positive metaphases of 12 patients and in Ph-negative metaphases of 5 patients. One patient showed trisomy 8 both in Ph-positive and in Ph-negative metaphases. The median follow-up after the detection of ACAs was 11.9 months. None of the patients carrying ACAs in their Ph-negative metaphases developed AP or BP; however, 7 out of 12 patients (58 %) having ACAs in their Ph-positive metaphases developed AP/BC at diagnosis or follow-up (p = 0.03). All the patients carrying ACAs in only Ph-negative metaphases achieved optimal response under tyrosine kinase inhibitor (TKI) therapy, whereas only 4 out of 12 patients (25 %) had optimal TKI response in patients with ACAs in Ph-positive metaphases (p = 0.009). The presence of ACAs in Ph-positive cells during TKI therapy may reflect genetic instability and therefore negatively affect OS. Conventional cytogenic analyses remain mandatory during follow-up of patients with CML under TKI therapy.
authors.affiliation: Department of Basic Oncology, Cancer Institute, Hacettepe University, 06100 Sihhiye, Ankara, Turkey. subozkurt@yahoo.com
authors.forename: Sureyya
authors.initials: S
authors.lastname: Bozkurt
authors.forename: Burak
authors.initials: B
authors.lastname: Uz
authors.forename: Yahya
authors.initials: Y
authors.lastname: Buyukasik
authors.forename: Ozlen
authors.initials: O
authors.lastname: Bektas
authors.forename: Ayten
authors.initials: A
authors.lastname: Inanc
authors.forename: Hakan
authors.initials: H
authors.lastname: Goker
authors.forename: Emin
authors.initials: E
authors.lastname: Kansu
mesh_terms: D059786:Abnormal Karyotype; D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use; D001549:Benzamides / Q000627:therapeutic use; D002869:Chromosome Aberrations; D020732:Cytogenetic Analysis; D005260:Female; D006801:Humans; D000068877:Imatinib Mesylate; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy* / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D010879:Piperazines / Q000627:therapeutic use; D011379:Prognosis; D011743:Pyrimidines / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D001549:Benzamides; D010879:Piperazines; D011743:Pyrimidines; D000068877:Imatinib Mesylate