Gene alterations involving the CRLF2‐JAK pathway and recurrent gene deletions in Down syndrome‐associated acute lymphoblastic leukemia in Japan. Issue 11 (16th July 2014)

• Record Type: Journal Article
• Authors: Hanada, Isamu; Terui, Kiminori; Ikeda, Fumika; Toki, Tsutomu; Kanezaki, Rika; Sato, Tomohiko; Kamio, Takuya; Kudo, Ko; Sasaki, Shinya; Takahashi, Yoshihiro; Hayashi, Yasuhide; Inukai, Takeshi; Kojima, Seiji; Koike, Kenichi; Kosaka, Yoshiyuki; Kobayashi, Masao; Imaizumi, Masue; Mitsui, Tetsuo; Hori, Hiroki; Hara, Junichi; Horibe, Keizo; Nagai, Jun‐ichi; Goto, Hiroaki; Ito, Etsuro
• Is Part Of: Genes, chromosomes & cancer. Volume 53:Issue 11(2014:Nov.)
• Page Start: 902
• Page End: 910
• Publication Date: 2014-07-16
• Subjects: Cancer -- Genetic aspects -- Periodicals; 616.994042
• DOI: 10.1002/gcc.22201
• Languages: English
• ISSNs: 1045-2257

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <p>In Western countries, gene alterations involving the CRLF2‐JAK signaling pathway are identified in approximately 50–60% of patients with Down syndrome‐associated acute lymphoblastic leukemia (DS‐ALL), and this pathway is considered a potential therapeutic target. The frequency of <italic>BTG1</italic> deletions in DS‐ALL is controversial. <italic>IKZF1</italic> deletions, found in 20–30% of DS‐ALL patients, are associated with a poor outcome and <italic>EBF1</italic> deletions are very rare (∼2%). We analyzed 38 patients to determine the frequencies and clinical implications of CRLF2‐JAK pathway genetic alterations and recurrent gene deletions in Japanese DS‐ALL patients. We confirmed a high incidence of <italic>P2RY8‐CRLF2</italic> (29%) and <italic>JAK2</italic> mutations (16%), though the frequency of <italic>P2RY8‐CRLF2</italic> was slightly lower than that in Western countries (∼50%). <italic>BTG1</italic> deletions were common in our cohort (25%). <italic>IKZF1</italic> deletions were detected in 25% of patients and associated with shorter overall survival (OS). <italic>EBF1</italic> deletions were found at an unexpectedly high frequency (16%), and at a significantly higher level in <italic>P2RY8‐CRLF2</italic>‐positive patients than in <italic>P2RY8‐CRLF2</italic>‐negative patients (44% vs. 4%, <italic>P</italic> = 0.015). Deletions of <italic>CDKN2A/B</italic> and <italic>PAX5</italic> were common in <italic>P2RY8‐CRLF2</italic>‐negative patients (48 and 39%, respectively) but not in <italic>P2RY8‐CRLF2</italic>‐positive patients (11% each). Associations between these genetic alterations and clinical characteristics were not observed except for inferior OS in patients with <italic>IKZF1</italic> deletions. These results suggest that differences exist between the genetic profiles of DS‐ALL patients in Japan and in Western countries, and that <italic>P2RY8‐CRLF2</italic> and <italic>EBF1</italic> deletions may cooperate in leukemogenesis in a subset of Japanese DS‐ALL patients. © 2014 Wiley Periodicals, Inc.</p> </abstract>