Annals of Hematology

, Volume 98, Issue 5, pp 1149–1157 | Cite as

Acute myeloid leukemia with t(8;16)(p11.2;p13.3)/KAT6A-CREBBP in adults

  • Wei Xie
  • Shimin Hu
  • Jie Xu
  • Zhining Chen
  • L. Jeffrey Medeiros
  • Guilin TangEmail author
Original Article


t(8;16)(p11.2;p13.3)/KAT6A-CREBBP is a rare recurrent cytogenetic abnormality associated with acute myeloid leukemia (AML). We report 15 cases with t(8;16)(p11.2;p13.3). All patients were adult and had AML: 13 women and 2 men, with a median age of 50 years. Ten patients had a history of malignancy and received cytotoxic therapies before therapy-related AML (t-AML), and five patients had de novo AML. All cases of AML showed monoblastic (n = 12) or myelomonocytic (n = 3) differentiation. Hemophagocytosis was observed in seven patients. All patients had t(8;16) in the stemline: seven had t(8;16) as the sole abnormality, two had one additional abnormality, and six had a complex karyotype. KAT6A/CREBBP rearrangement was confirmed by fluorescence in situ hybridization in 13 patients who had material available for analysis. All patients received induction chemotherapy, and 11 achieved complete remission after first induction. At the time of last follow-up, nine patients (eight t-AML and one de novo AML) died and six were alive, with a median overall survival of 18.2 months. The patients with de novo AML and/or patients with non-complex karyotype showed an “undefined” overall survival. We conclude that t(8;16)(p11.2;p13.3) commonly exhibits monoblastic or myelomonocytic differentiation and commonly arises in patients with a history of cancer treated with cytotoxic therapies. Patients with de novo AML with t(8;16) or t-AML with t(8;16) without adverse prognostic factors (e.g., complex karyotype) have a good outcome.


Acute myeloid leukemia t(8;16)(p11.2;p13.3) KAT6A CREBBP Therapy-related 


Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

This is a retrospective study and all procedures performed in the study were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent

Informed consent was obtained from all participants included in the study.

Supplementary material

277_2019_3637_MOESM1_ESM.docx (14 kb)
ESM 1 (DOCX 13 kb)
277_2019_3637_MOESM2_ESM.docx (20 kb)
ESM 2 (DOCX 20 kb)


  1. 1.
    Haferlach T et al (2009) AML with translocation t(8;16)(p11;p13) demonstrates unique cytomorphological, cytogenetic, molecular and prognostic features. Leukemia 23:934–943. CrossRefGoogle Scholar
  2. 2.
    Mitelman F, Johansson B, Mertens F. Mitelman database of chromosome aberrations and gene fusions in cancer. Available at: Accessed Dec 2018
  3. 3.
    Gervais C, Murati A, Helias C, Struski S, Eischen A, Lippert E, Tigaud I, Penther D, Bastard C, Mugneret F, Poppe B, Speleman F, Talmant P, VanDen Akker J, Baranger L, Barin C, Luquet I, Nadal N, Nguyen-Khac F, Maarek O, Herens C, Sainty D, Flandrin G, Birnbaum D, Mozziconacci MJ, Lessard M, Groupe Francophone de Cytogenetique H (2008) Acute myeloid leukaemia with 8p11 (MYST3) rearrangement: an integrated cytologic, cytogenetic and molecular study by the groupe francophone de cytogenetique hematologique. Leukemia 22(8):1567–1575.
  4. 4.
    Diab A, Zickl L, Abdel-Wahab O, Jhanwar S, Gulam MA, Panageas KS, Patel JP, Jurcic J, Maslak P, Paietta E, Mangan JK, Carroll M, Fernandez HF, Teruya-Feldstein J, Luger SM, Douer D, Litzow MR, Lazarus HM, Rowe JM, Levine RL, Tallman MS (2013) Acute myeloid leukemia with translocation t(8;16) presents with features which mimic acute promyelocytic leukemia and is associated with poor prognosis. Leuk Res 37(1):32–36.
  5. 5.
    Gupta A, Patnaik MM, Naina HV (2014) MYST3/CREBBP rearranged acute myeloid leukemia after adjuvant chemotherapy for breast cancer. Case Rep Oncol Med 2014:361748.
  6. 6.
    Chakraborty S, Adams J, Nassiri M, Vance GH (2014) Therapy-related myeloid neoplasm with bone marrow involvement, myelosarcoma, and a t(8;16)(p11.2;p13.3)-a case report. Cancer Genet 207(10–12):511–515.
  7. 7.
    Blieden C, Fan YS, Chapman JR, Vega F (2014) De novo acute myeloid leukemia with monocytoid blasts and erythrophagocytosis. Clin Case Rep 2:333–335. CrossRefGoogle Scholar
  8. 8.
    Andrade FG, Noronha EP, Baseggio RM, Fonseca TC, Freire BM, Quezado Magalhaes IM, Zalcberg IR, Pombo-de-Oliveira MS (2016) Identification of the MYST3-CREBBP fusion gene in infants with acute myeloid leukemia and hemophagocytosis. Rev Bras Hematol Hemoter 38(4):291–297.
  9. 9.
    Coenen EA, Zwaan CM, Reinhardt D, Harrison CJ, Haas OA, de Haas V, Mihal V, De Moerloose B, Jeison M, Rubnitz JE, Tomizawa D, Johnston D, Alonzo TA, Hasle H, Auvrignon A, Dworzak M, Pession A, van der Velden VH, Swansbury J, Wong KF, Terui K, Savasan S, Winstanley M, Vaitkeviciene G, Zimmermann M, Pieters R, van den Heuvel-Eibrink MM (2013) Pediatric acute myeloid leukemia with t(8;16)(p11;p13), a distinct clinical and biological entity: a collaborative study by the International-Berlin-Frankfurt-Munster AML-study group. Blood 122(15):2704–2713.
  10. 10.
    Barrett R, Morash B, Roback D, Pambrun C, Marfleet L, Ketterling RP, Harrison K, Berman JN (2017) FISH identifies a KAT6A/CREBBP fusion caused by a cryptic insertional t(8;16) in a case of spontaneously remitting congenital acute myeloid leukemia with a normal karyotype. Pediatr Blood Cancer 64(8).
  11. 11.
    Wong KF, Yuen HL, Siu LL, Pang A, Kwong YL (2008) t(8;16)(p11;p13) predisposes to a transient but potentially recurring neonatal leukemia. Hum Pathol 39(11):1702–1707. CrossRefGoogle Scholar
  12. 12.
    Roberts I, Fordham NJ, Rao A, Bain BJ (2018) Neonatal leukaemia. Br J Haematol 182(2):170–184. CrossRefGoogle Scholar
  13. 13.
    Kitabayashi I, Aikawa Y, Nguyen LA, Yokoyama A, Ohki M (2001) Activation of AML1-mediated transcription by MOZ and inhibition by the MOZ-CBP fusion protein. EMBO J 20:7184–7196. CrossRefGoogle Scholar
  14. 14.
    Jacobson S, Pillus L (1999) Modifying chromatin and concepts of cancer. Curr Opin Genet Dev 9(2):175–184. CrossRefGoogle Scholar
  15. 15.
    Borrow J, Stanton VP, Jr., Andresen JM, Becher R, Behm FG, Chaganti RS, Civin CI, Disteche C, Dube I, Frischauf AM, Horsman D, Mitelman F, Volinia S, Watmore AE, Housman DE (1996) The translocation t(8;16)(p11;p13) of acute myeloid leukaemia fuses a putative acetyltransferase to the CREB-binding protein. Nat Genet 14(1):33–41.
  16. 16.
    Swerdlow SH, Campo E, Harris NL et al (eds) (2017) WHO classification of tumours of haematopoietic and lymphoid tissues, revised 4th ed. IARC, LyonGoogle Scholar
  17. 17.
    McNerney ME, Godley LA, Le Beau MM (2017) Therapy-related myeloid neoplasms: when genetics and environment collide. Nat Rev Cancer 17(9):513–527. CrossRefGoogle Scholar
  18. 18.
    Le Deley MC, Suzan F, Cutuli B, Delaloge S, Shamsaldin A, Linassier C, Clisant S, de Vathaire F, Fenaux P, Hill C (2007) Anthracyclines, mitoxantrone, radiotherapy, and granulocyte colony-stimulating factor: risk factors for leukemia and myelodysplastic syndrome after breast cancer. J Clin Oncol 25(3):292–300.
  19. 19.
    Ouyang J, Goswami M, Tang G, Peng J, Ravandi F, Daver N, Routbort M, Konoplev S, Lin P, Medeiros LJ, Jorgensen JL, Wang SA (2015) The clinical significance of negative flow cytometry immunophenotypic results in a morphologically scored positive bone marrow in patients following treatment for acute myeloid leukemia. Am J Hematol 90(6):504–510.
  20. 20.
    Tang G, Hu S, Wang SA, Xie W, Lin P, Xu J, Toruner G, Zhao M, Gu J, Doty M, Li S, Medeiros LJ, Tang Z (2018) t(3;8)(q26.2;q24) Often leads to MECOM/MYC rearrangement and is commonly associated with therapy-related myeloid neoplasms and/or disease progression. J Mol Diagn.
  21. 21.
    Marneth AE, Prange KHM, Al Hinai ASA, Bergevoet SM, Tesi N, Janssen-Megens EM, Kim B, Sharifi N, Yaspo ML, Kuster J, Sanders MA, Stoetman ECG, Knijnenburg J, Arentsen-Peters T, Zwaan CM, Stunnenberg HG, van den Heuvel-Eibrink MM, Haferlach T, Fornerod M, Jansen JH, Valk PJM, van der Reijden BA, Martens JHA (2018) C-terminal BRE overexpression in 11q23-rearranged and t(8;16) acute myeloid leukemia is caused by intragenic transcription initiation. Leukemia 32(3):828–836.
  22. 22.
    Feng L, Huang J, Chen J (2009) MERIT40 facilitates BRCA1 localization and DNA damage repair. Genes Dev 23:719–728. CrossRefGoogle Scholar
  23. 23.
    Noordermeer SM, Sanders MA, Gilissen C, Tonnissen E, van der Heijden A, Dohner K, Bullinger L, Jansen JH, Valk PJ, van der Reijden BA (2011) High BRE expression predicts favorable outcome in adult acute myeloid leukemia, in particular among MLL-AF9-positive patients. Blood 118(20):5613–5621.
  24. 24.
    Balgobind BV, Zwaan CM, Reinhardt D, Arentsen-Peters TJ, Hollink IH, de Haas V, Kaspers GJ, de Bont ES, Baruchel A, Stary J, Meyer C, Marschalek R, Creutzig U, den Boer ML, Pieters R, van den Heuvel-Eibrink MM (2010) High BRE expression in pediatric MLL-rearranged AML is associated with favorable outcome. Leukemia 24(12):2048–2055.
  25. 25.
    Sahin FI et al (2006) t(8;16) AML developed subsequent to breast cancer therapy. Hematology 11:153–155.
  26. 26.
    Rowley JD, Reshmi S, Sobulo O, Musvee T, Anastasi J, Raimondi S, Schneider NR, Barredo JC, Cantu ES, Schlegelberger B, Behm F, Doggett NA, Borrow J, Zeleznik-Le N (1997) All patients with the T(11;16)(q23;p13.3) that involves MLL and CBP have treatment-related hematologic disorders. Blood 90(2):535–541Google Scholar
  27. 27.
    Zandecki M, Lai JL, Mazingue F, Lepelley P, Chassaing O, Farriaux JP, Deminatti M, Cosson A (1988) Congenital acute monoblastic leukemia with double translocation (8;16) (p11;p13) and (16;20) (q13;p13). Nouv Rev Fr Hematol 30(4):247–250Google Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Departments of HematopathologyThe University of Texas MD Anderson Cancer CenterHoustonUSA

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