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International Journal of Hematology

, Volume 108, Issue 3, pp 312–318 | Cite as

Copy number abnormality of acute lymphoblastic leukemia cell lines based on their genetic subtypes

  • Chihiro Tomoyasu
  • Toshihiko Imamura
  • Toshihiro Tomii
  • Mio Yano
  • Daisuke Asai
  • Hiroaki Goto
  • Akira Shimada
  • Masashi Sanada
  • Shotaro Iwamoto
  • Junko Takita
  • Masayoshi Minegishi
  • Takeshi Inukai
  • Kanji Sugita
  • Hajime Hosoi
Original Article

Abstract

In this study, we performed genetic analysis of 83 B cell precursor acute lymphoblastic leukemia (B-ALL) cell lines. First, we performed multiplex ligation-dependent probe amplification analysis to identify copy number abnormalities (CNAs) in eight genes associated with B-ALL according to genetic subtype. In Ph+ B-ALL cell lines, the frequencies of IKZF1, CDKN2A/2B, BTG1, and PAX5 deletion were significantly higher than those in Ph B-ALL cell lines. The frequency of CDKN2A/2B deletion in KMT2A rearranged cell lines was significantly lower than that in non-KMT2A rearranged cell lines. These findings suggest that CNAs are correlated with genetic subtype in B-ALL cell lines. In addition, we determined that three B-other ALL cell lines had IKZF1 deletions (YCUB-5, KOPN49, and KOPN75); we therefore performed comprehensive genetic analysis of these cell lines. YCUB-5, KOPN49, and KOPN75 had P2RY8-CRLF2, IgH-CRLF2, and PAX5-ETV6 fusions, respectively. Moreover, targeted capture sequencing revealed that YCUB-5 had JAK2 R683I and KRAS G12D, and KOPN49 had JAK2 R683G and KRAS G13D mutations. These data may contribute to progress in the field of leukemia research.

Keywords

Copy number abnormality Acute lymphoblastic leukemia cell line CDKN2A CDKN2B BTG1 IKZF1 

Notes

Acknowledgements

SU-Ph2 was established at Kinki University School of Medicine, Osaka, and provided in 2010 (Dr. Y. Maeda). TCCY was established at Tochigi Cancer Center and provided in 2011 (Dr. Y. Sato). HALO1 and SK9 were established at Tokyo Medical University, Tokyo, and provided in 1997 (Dr. T. Look in Dana-Farber Cancer Institute, Boston, MA) and in 2012 (Dr. S. Okabe), respectively. Endokun was established at Iwate Medical University, Morioka, and provided in 1997 (Dr. M. Endo). Kasumi2 established at Hiroshima University, Hiroshima, and provided in 2010 (Dr. T. Inaba).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest. A summary of relevant information will be published with the manuscript.

Supplementary material

12185_2018_2474_MOESM1_ESM.doc (264 kb)
Supplementary material 1 (DOC 264 KB)

References

  1. 1.
    Liem NL, Papa RA, Milross CG, Schmid MA, Tajbakhsh M, Choi S, et al. Characterization of childhood acute lymphoblastic leukemia xenograft models for the preclinical evaluation of new therapies. Blood. 2004;103(10):3905–14.CrossRefPubMedGoogle Scholar
  2. 2.
    McCormack E, Bruserud O, Gjertsen BT. Animal models of acute myelogenous leukaemia—development, application and future perspectives. Leukemia. 2005;19(5):687–706.CrossRefPubMedGoogle Scholar
  3. 3.
    Maude SL, Tasian SK, Vincent T, Hall JW, Sheen C, Roberts KG, et al. Targeting JAK1/2 and mTOR in murine xenograft models of Ph-like acute lymphoblastic leukemia. Blood. 2012;120(17):3510–8.CrossRefPubMedPubMedCentralGoogle Scholar
  4. 4.
    Den Boer ML, van Slegtenhorst M, De Menezes RX, Cheok MH, Buijs-Gladdines JG, Peters ST, et al. A subtype of childhood acute lymphoblastic leukaemia with poor treatment outcome: a genome-wide classification study. Lancet Oncol. 2009;10(2):125–34.CrossRefGoogle Scholar
  5. 5.
    Roberts KG, Li Y, Payne-Turner D, Harvey RC, Yang YL, Pei D, McCastlain K, et al. Targetable kinase-activating lesions in Ph-like acute lymphoblastic leukemia. New Engl J of Med. 2014;371:1005–15.CrossRefGoogle Scholar
  6. 6.
    Hirose M, Minato K, Tobinai K, Ohira M, Ise T, Watanabe S, Shimoyama M, Taniwaki M, Abe T. A novel pre-T cell line derived from acute lymphoblastic leukemia. Gan. 1982;73(4):600–5.PubMedGoogle Scholar
  7. 7.
    Minegishi M, Tsuchiya S, Minegishi N, Konno T. Establishment of five human malignant non-T lymphoid cell lines and mixed lymphocyte-tumor reaction. Tohoku J Exp Med. 1987;151:283–92.CrossRefPubMedGoogle Scholar
  8. 8.
    Kawamura M, Kikuchi A, Kobayashi S, Hanada R, Yamamoto K, Horibe K, et al. Mutations of the p53 and ras genes in childhood t(1;19)-acute lymphoblastic leukemia. Blood. 1995;85(9):2546–52.PubMedGoogle Scholar
  9. 9.
    Ariyasu T, Matsuo Y, Harashima A, Nakamura S, Takaba S, Tsubota T, et al. Establishment and characterization of “biphenotypic” acute leukemia cell lines with a variant Ph translocation t(9;22;10) (q34;q11;q22). Hum Cell. 1998;11(1):43–50.PubMedGoogle Scholar
  10. 10.
    Kang J, Kisenge RR, Toyoda H, Tanaka S, Bu J, Azuma E, et al. Chemical sensitization and regulation of TRAIL-induced apoptosis in a panel of B-lymphocytic leukaemia cell lines. Br J Haematol. 2003;123:921–32.CrossRefPubMedGoogle Scholar
  11. 11.
    Goto H, Naruto T, Tanoshima R, Kato H, Yokosuka T, Yanagimachi M, et al. Chemo-sensitivity in a panel of B-cell precursor acute lymphoblastic leukemia cell lines, YCUB series, derived from children. Leu Res. 2009;33:1386–91.CrossRefGoogle Scholar
  12. 12.
    Hirase C, Maeda Y, Takai S, Kanamaru A. Hypersensitivity of Ph-positive lymphoid cell lines to rapamycin: possible clinical application of mTOR inhibitor. Leuk Res. 2009;33:450–9.CrossRefPubMedGoogle Scholar
  13. 13.
    Shiotsu Y, Kiyoi H, Ishikawa Y, Tanizaki R, Shimizu M, Umehara H, et al. KW-2449, a novel multikinase inhibitor, suppresses the growth of leukemia cells with FLT3 mutations or T315I-mutated BCR/ABL translocation. Blood. 2009;114:1607–17.CrossRefPubMedGoogle Scholar
  14. 14.
    Hirose K, Inukai T, Kikuchi J, Furukawa Y, Ikawa T, Kawamoto H, et al. Aberrant induction of LMO2 by the E2A-HLF chimeric transcription factor and its implication in leukemogenesis of B-precursor ALL with t(17;19). Blood 2010;116:962–70.CrossRefGoogle Scholar
  15. 15.
    Okabe S, Tauchi T, Ohyashiki K. Establishment of a new Philadelphia chromosome-positive acute lymphoblastic leukemia cell line (SK-9) with T315I mutation. Exp Hematol. 2010;38:765–72.CrossRefPubMedGoogle Scholar
  16. 16.
    Akbari Moqadam F, Boer JM, Lange-Turenhout EA, Pieters R, den Boer ML. Altered expression of miR-24, miR-126 and miR-365 does not affect viability of childhood TCF3-rearranged leukemia cells. Leukemia. 2014;28(5):1008–14.CrossRefPubMedGoogle Scholar
  17. 17.
    Asai D, Imamura T, Suenobu S, Saito A, Hasegawa D, Deguchi T, et al. IKZF1 deletion is associated with a poor outcome in pediatric B-cell precursor acute lymphoblastic leukemia in Japan. Cancer Med. 2013;2:412–9.CrossRefPubMedPubMedCentralGoogle Scholar
  18. 18.
    Roberts KG, Morin RD, Zhang J, Hirst M, Zhao Y, Su X, et al. Genetic alterations activating kinase and cytokine receptor signaling in high-risk acute lymphoblastic leukemia. Cancer Cell. 2012;22(2):153–66.CrossRefPubMedPubMedCentralGoogle Scholar
  19. 19.
    Ishida H, Kanamitsu K, Washio K, Muraoka M, Sakakibara K, Matsubara T, et al. Relapsed infant MLL-rearranged acute lymphoblastic leukemia with additional genetic alterations. Pediatr Blood Cancer. 2016;63(11):2059–60.CrossRefPubMedGoogle Scholar
  20. 20.
    Schwab CJ, Chilton L, Morrison H, Jones L, Al-Shehhi H, Erhorn A, et al. Genes commonly deleted in childhood B-cell precursor acute lymphoblastic leukemia: association with cytogenetics and clinical features. Haematologica. 2013;98(7):1081–8.CrossRefPubMedPubMedCentralGoogle Scholar
  21. 21.
    Imamura T, Kiyokawa N, Kato M, Imai C, Okamoto Y, Yano M, et al. Characterization of pediatric Philadelphia-negative B-cell precursor acute lymphoblastic leukemia with kinase fusions in Japan. Blood Cancer J. 2016;6:e419.CrossRefPubMedPubMedCentralGoogle Scholar
  22. 22.
    Reshmi SC, Harvey RC, Roberts KG, Stonerock E, Smith A, Jenkins H, et al. Targetable kinase gene fusions in high-risk B-ALL: a study from the Children’s Oncology Group. Blood. 2017;129(25):3352–61.PubMedPubMedCentralGoogle Scholar
  23. 23.
    Kim WY, Sharpless NE. The regulation of INK4/ARF in cancer and aging. Cell. 2006;127(2):265–75.CrossRefPubMedGoogle Scholar
  24. 24.
    van Zutven LJ, van Drunen E, de Bont JM, Wattel MM, Den Boer ML, Pieters R, et al. CDKN2 deletions have no prognostic value in childhood precursor-B acute lymphoblastic leukaemia. Leukemia. 2005;19(7):1281–4.CrossRefPubMedGoogle Scholar
  25. 25.
    Braun M, Pastorczak A, Fendler W, Madzio J, Tomasik B, Taha J, et al. Biallelic loss of CDKN2A is associated with poor response to treatment in pediatric acute lymphoblastic leukemia. Leuk Lymphoma. 2017;58(5):1162–71.CrossRefPubMedGoogle Scholar
  26. 26.
    Churchman ML, Low J, Qu C, Paietta EM, Kasper LH, Chang Y, et al. Efficacy of retinoids in IKZF1-mutated BCR-ABL1 acute lymphoblastic leukemia. Cancer Cell. 2015;28(3):343–56.CrossRefPubMedPubMedCentralGoogle Scholar
  27. 27.
    Rouault JP, Rimokh R, Tessa C, Paranhos G, Ffrench M, Duret L, et al. BTG1, a member of a new family of antiproliferative genes. EMBO J. 1992;11(4):1663–70.PubMedPubMedCentralCrossRefGoogle Scholar
  28. 28.
    Scheijen B, Boer JM, Marke R, Tijchon E, van Ingen Schenau D, Waanders E, et al. Tumor suppressors BTG1 and IKZF1 cooperate during mouse leukemia development and increase relapse risk in B-cell precursor acute lymphoblastic leukemia patients. Haematologica. 2017;102(3):541–51.CrossRefPubMedPubMedCentralGoogle Scholar
  29. 29.
    Cazzaniga G, Daniotti M, Tosi S, Giudici G, Aloisi A, Pogliani E, et al. The paired box domain gene PAX5 is fused to ETV6/TEL in an acute lymphoblastic leukemia case. Cancer Res. 2001;61(12):4666–70.PubMedGoogle Scholar
  30. 30.
    Strehl S, König M, Dworzak MN, Kalwak K, Haas OA. PAX5/ETV6 fusion defines cytogenetic entity dic(9;12)(p13;p13). Leukemia. 2003;17(6):1121–3.CrossRefPubMedGoogle Scholar
  31. 31.
    Fazio G, Cazzaniga V, Palmi C, Galbiati M, Giordan M, te Kronnie G, et al. PAX5/ETV6 alters the gene expression profile of precursor B cells with opposite dominant effect on endogenous PAX5. Leukemia. 2013;27(4):992–5.CrossRefPubMedGoogle Scholar
  32. 32.
    Chen IM, Harvey RC, Mullighan CG, Gastier-Foster J, Wharton W, Kang H, et al. Outcome modeling with CRLF2, IKZF1, JAK, and minimal residual disease in pediatric acute lymphoblastic leukemia: a Children’s Oncology Group study. Blood. 2012;119(15):3512–22.CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© The Japanese Society of Hematology 2018

Authors and Affiliations

  • Chihiro Tomoyasu
    • 1
    • 2
  • Toshihiko Imamura
    • 1
  • Toshihiro Tomii
    • 1
  • Mio Yano
    • 3
  • Daisuke Asai
    • 4
  • Hiroaki Goto
    • 5
  • Akira Shimada
    • 6
  • Masashi Sanada
    • 7
  • Shotaro Iwamoto
    • 8
  • Junko Takita
    • 9
  • Masayoshi Minegishi
    • 10
  • Takeshi Inukai
    • 11
  • Kanji Sugita
    • 11
  • Hajime Hosoi
    • 1
  1. 1.Department of Pediatrics, Graduate School of Medical ScienceKyoto Prefectural University of MedicineKyotoJapan
  2. 2.Department of PediatricsNational Hospital Organization Maizuru Medical CenterMaizuruJapan
  3. 3.Department of PediatricsKyoto City HospitalKyotoJapan
  4. 4.Department of PediatricsJapanese Red Cross Kyoto Daini HospitalKyotoJapan
  5. 5.Division of Hemato-Oncology and Regenerative MedicineKanagawa Children’s Medical CenterYokohamaJapan
  6. 6.Department of Pediatric Hematology/OncologyOkayama University HospitalOkayamaJapan
  7. 7.Clinical Research CenterNational Hospital Organization Nagoya Medical CenterNagoyaJapan
  8. 8.Department of PediatricsMie University Graduate School of MedicineTsuJapan
  9. 9.Department of Pediatrics, Graduate School of MedicineThe University of TokyoTokyoJapan
  10. 10.Japanese Red Cross Fukushima Blood CenterOkumaJapan
  11. 11.Department of PediatricsYamanashi UniversityKofuJapan

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