Genetic Events in Ikaros Gene Family (IKZF1 and IKZF2) in Pediatric T-Cell Lymphoblastic Leukemia/Lymphoma

• Published in: Blood 2012-11, Vol.120 (21), p.4622-4622
• Main Authors: Narita, Atsushi, Muramatsu, Hideki, Yoshida, Nao, Sakaguchi, Hirotoshi, Doisaki, Sayoko, Hama, Asahito, Nakanishi, Koji, Takahashi, Yoshiyuki, Miyajima, Yuji, Matsumoto, Kimikazu, Kato, Koji, Kojima, Seiji
• Format: Article
• Language: English
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood.V120.21.4622.4622

Abstract 4622 The Ikaros gene family, which includes Ikaros (IKZF1), Helios (IKZF2), and Aiolos (IKZF3), is a primary regulator of lymphocyte differentiation and is involved in the development of acute lymphoblastic leukemia (ALL). In particular, loss of IKZF1 is primarily associated with T-cell ALL (T-ALL) development in mouse models. Moreover, Helios expression has been detected in early T-cell lineage and is involved in human lymphoid proliferative disease. We sought to determine whether the Ikaros gene family is associated with leukemogenesis in T-ALL and T-cell non-Hodgkin lymphoma (T-NHL) in Japanese children. Fifty-eight Japanese children (39 boys and 19 girls; age, G, p.N159S; patient number 41) who was diagnosed with primary immune deficiency after birth. She received regular immunoglobulin replacement therapy just before the development of T-ALL at 13 years of age. Her IKZF1 mutation was confirmed as a germline mutation by sequencing of genomic DNA from her fingernails. In the IKZF1 null mouse model, Ikaros inactivation is closely linked to T-ALL development, which is highly associated with acquisition of a somatic NOTCH1 mutation. As in the