Identification of a homozygous JAK3 V674A mutation caused by acquired uniparental disomy in a relapsed early T-cell precursor ALL patient
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- 作者：Sachiko Kawashima-Goto (1)
Toshihiko Imamura (1)
Masafumi Seki (2)
Motohiro Kato (2)
Kenichi Yoshida (3)
Atsuya Sugimoto (1)
Daisuke Kaneda (1)
Atsushi Fujiki (4)
Mitsuru Miyachi (1)
Takuya Nakatani (4) (5)
Shinya Osone (1)
Hiroyuki Ishida (1) (5)
Tomohiko Taki (6)
Junko Takita (2)
Yuichi Shiraishi (7)
Kenichi Chiba (7)
Hiroko Tanaka (8)
Satoru Miyano (7) (8)
Seishi Ogawa (3)
Hajime Hosoi (1)
1. Department of Pediatrics ; Kyoto Prefectural University of Medicine ; Graduate School of Medical Science ; Kajii-cho Hirokoji ; Kamigyo-ku ; Kyoto ; 602-8566 ; Japan
2. Department of Pediatrics ; The University of Tokyo ; Tokyo ; Japan
3. Department of Pathology and Tumor Biology ; Kyoto University ; Kyoto ; Japan
4. Department of Pediatrics ; National Hospital Organization Maizuru Medical Center ; Maizuru ; Japan
5. Department of Pediatrics ; Matsushita Memorial Hospital ; Moriguchi ; Japan
6. Department of Molecular Diagnostics and Therapeutics ; Kyoto Prefectural University of Medicine ; Graduate School of Medical Science ; Kyoto ; Japan
7. Laboratory of DNA Information Analysis ; Human Genome Center ; Institute of Medical Science ; The University of Tokyo ; Tokyo ; Japan
8. Laboratory of Sequence Analysis ; Human Genome Center ; Institute of Medical Science ; The University of Tokyo ; Tokyo ; Japan - 关键词：ETP ; ALL ; JAK3 ; Acquired UPD ; SNP array ; Whole ; exome sequencing
- 刊名：International Journal of Hematology
- 出版年：2015
- 出版时间：April 2015
- 年：2015
- 卷：101
- 期：4
- 页码：411-416
- 全文大小：367 KB
- 参考文献：1. Coustan-Smith, E, Mullighan, CG, Onciu, M, Behm, FG, Raimondi, SC, Pei, D (2009) Early T-cell precursor leukemia: a subtype of very high-risk acute lymphoblastic leukemia. Lancet Oncol 10: pp. 147-156 2045(08)70314-0" target="_blank" title="It opens in new window">CrossRef
2. Zhang, J, Ding, L, Holmfeldt, L, Wu, G, Heatley, SL, Payne-Turner, D (2012) The genetic basis of early T-cell precursor acute lymphoblastic leukemia. Nature 481: pp. 157-163 25" target="_blank" title="It opens in new window">CrossRef
3. Choi, YL, Kaneda, R, Wada, T, Fujiwara, S, Soda, M, Watanabe, H (2007) Identification of a constitutively active mutant of JAK3 by retroviral expression screening. Leuk Res 31: pp. 203-209 2006.05.006" target="_blank" title="It opens in new window">CrossRef
4. Suzuki, N, Yumura-Yagi, K, Yoshida, M, Hara, J, Nishimura, S, Kudoh, T (2010) Outcome of childhood acute lymphoblastic leukemia with induction failure treated by the Japan Associated of Childhood Leukemia study (JACLS) ALL F-protocol. Pediatr Blood Cancer 54: pp. 71-78 2/pbc.22217" target="_blank" title="It opens in new window">CrossRef
5. Yoshida, K, Toki, T, Okuno, Y, Kanezaki, R, Shiraishi, Y, Sato-Otsubo, A (2013) The landscape of somatic mutations in Down syndrome-related myeloid disorders. Nat Genet 45: pp. 1293-1299 2759" target="_blank" title="It opens in new window">CrossRef
6. Lahortiga, I, Keersmaecker, K, Vlierberghe, P, Graux, C, Cauwelier, B, Lambert, F (2007) Duplication of the MYB oncogene in T cell acute lymphoblastic leukemia. Nat Genet 39: pp. 593-595 2025" target="_blank" title="It opens in new window">CrossRef
7. Witthuhn, BA, Silvenoinen, O, Miura, O, Lai, KS, Cwik, C, Liu, ET (1994) Involvement of the JAK-3 Janus kinase in signaling by interleukins 2 and 4 in lymphoid and myeloid cells. Nature 370: pp. 153-157 CrossRef
8. Macchi, P, Villa, A, Giliani, S, Sacco, MG, Frattini, A, Porta, F (1995) Mutations of Jak-3 gene in patients with autosomal severe combined immune deficiency (SCID). Nature 377: pp. 65-68 CrossRef
9. Kalender Atak, Z, Keerskaecker, K, Gianfelici, V, Geerdens, E, Vandepoel, R, Pauwels, D (2012) High accuracy mutation detection in leukemia on a selected panel of cancer genes. PLoS One 7: pp. e38463 CrossRef
10. Bergmann, AK, Schneppenheim, S, Seifert, M, Betts, MJ, Haake, A, Lopez, C (2014) Recurrent mutation of JAK3 in T-cell prolymphocytic leukemia. Genes Chromosomes Cancer 53: pp. 309-316 2/gcc.22141" target="_blank" title="It opens in new window">CrossRef
11. Raghavan, M, Smith, LL, Lilllington, DM, Chaplin, T, Kakkas, I, Molloy, G (2008) Segmental uniparental disomy is a commonly acquired genetic event in relapsed acute myeloid leukemia. Blood 112: pp. 814-821 2/blood-2008-01-132431" target="_blank" title="It opens in new window">CrossRef - 刊物主题：Hematology; Oncology;
- 出版者：Springer Japan
- ISSN：1865-3774
文摘
Investigation of genetic alterations associated with relapse in acute lymphoblastic leukemia (ALL) may help to identify druggable targets for specific therapies. Early T-cell precursor ALL (ETP-ALL) is a subtype of T-ALL with poor prognosis. Although the genetic landscape of ETP-ALL has been determined, genetic alterations related to the relapse of ETP-ALL have not been fully investigated. Here, we report the first patient with relapsed pediatric ETP-ALL to exhibit a homozygous JAK3 activating mutation, V674A, caused by acquired uniparental disomy (UPD). Single nucleotide polymorphism array analysis revealed acquired UPD (aUPD) at the 19p13.3-p12 locus only in leukemic cells at relapse. Sanger sequence of the JAK3 gene, which was located at 19p13.1 and frequently mutated in ETP-ALL, was performed in paired leukemic samples to determine homozygous JAK3 V674A mutation only in relapsed leukemic cells. In contrast, leukemic cells at initial diagnosis harbored hemizygous JAK3 V674A mutation. Further, whole-exome sequencing revealed mutations in 18 genes only in relapsed samples, although none of these was recurrent in T-ALL. These findings suggest that aUPD at 19p13.1 is partly associated with relapse in this patient. Pharmacological inhibition of JAK3 may be therapeutic in such cases.