Loss of the Y chromosome in Philadelphia-positive cells predicts a poor response of chronic myeloid leukemia patients to imatinib mesylate therapy

• Published in: Haematologica (Roma) Vol. 95; no. 9; pp. 1604 - 1607
• Main Authors: LIPPERT, Eric, ETIENNE, Gabriel, FORT, Marie-Pierre, LEGROS, Laurence, ECLACHE, Virginie, MAHON, Francois-Xavier, MOZZICONACCI, Marie-Joelle, LAIBE, Sophy, GERVAIS, Carine, GIRAULT, Stéphane, GACHARD, Nathalie, TIGAUD, Isabelle, DASTUGUE, Nicole, HUGUET, François
• Format: Journal Article
• Language: English
• Published: Pavia Ferrata Storti Foundation 01.09.2010
• Subjects: Benzamides; Biological and medical sciences; Brief Report; Chromosome Aberrations; Chromosomes, Human, Y; Hematologic and hematopoietic diseases; Humans; Imatinib Mesylate; Leukemia, Myelogenous, Chronic, BCR-ABL Positive - diagnosis; Leukemia, Myelogenous, Chronic, BCR-ABL Positive - drug therapy; Leukemia, Myelogenous, Chronic, BCR-ABL Positive - genetics; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Male; Medical sciences; Piperazines - therapeutic use; Prognosis; Pyrimidines - therapeutic use; Retrospective Studies; Survival Analysis; Chromosomal aberration; Antineoplastic agent; Myeloproliferative syndrome; Abnormal chromosome C9; loss; Abnormal chromosome G22; chronic myeloid leukemia; Protein-tyrosine kinase; Philadelphia-positive; Human; Imatinib; Hematology; Enzyme; Tyrosine kinase inhibitor; Transferases; Y chromosome; Enzyme inhibitor; Chronic myelogenous leukemia; Malignant hemopathy; Y-Chromosome; Philadelphia chromosome; Treatment; Abnormal chromosome; Predictive factor; Cancer
• ISSN: 0390-6078; 1592-8721
• DOI: 10.3324/haematol.2009.019109

In chronic myeloid leukemia (CML), cytogenetic abnormalities found in addition to the t(9;22) translocation may impact the response to therapy. Loss of the Y chromosome is generally overlooked in this context, owing to its relatively frequent occurrence in healthy elderly patients. In this multicenter retrospective study, the outcome after imatinib treatment of 30 CML patients with karyotype showing Y chromosome loss (Y-) was compared to 30 Y+ control males diagnosed and treated at the same time in the same institutions. Y- patients had significantly delayed cytogenetic and molecular responses, lower event-free survival and shorter overall survival than Y+ patients. The negative impact of this abnormality was particularly marked when it occurred in a sub-clone (clonal evolution) rather than in all mitoses. These data indicate that loss of the Y chromosome should be taken into account in the prognostic evaluation of chronic myelogenous leukemia patients.