Complex karyotype (CK) with ≥ 3 abnormalities is detected in 10–12% of patients with acute myeloid leukemia (AML) and associated with poor prognosis. The most common unbalanced abnormalities found in CK result in loss of material from the 5q, 7q, and/or 17p chromosome arms. The presence of 5q, 7q, and/or 17p abnormalities denotes typical CK and their absence denotes atypical CK. Since molecular features of CK-AML are not well characterized, we investigated mutational status of 81 leukemia/cancer-associated genes in 160 clinically well-characterized patients. They included 136 patients with ≥ 3 exclusively unbalanced chromosome abnormalities, 96 of whom had a typical CK and 40 atypical CK, and 24 patients with ≥ 1 balanced abnormality in addition to ≥ 2 unbalanced ones. Patients with atypical CK-AML differed from those with typical CK-AML: they carried TP53 mutations less often (P < 0.001) and more often PHF6 (P = 0.008), FLT3-TKD (P = 0.02), MED12 (P = 0.02), and NPM1 (P = 0.02) mutations. They were younger (P= 0.007), had higher WBC (P = 0.001) and percentages of marrow (P < 0.001) and blood (P = 0.006) blasts, higher complete remission rates (P = 0.02), and longer overall survival (P < 0.001), thus indicating that atypical and typical CK-AMLs constitute distinct disease subtypes. We also identified smaller patient subsets within both typical and atypical CK-AML that differed molecularly and clinically.

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The authors thank the patients who participated in clinical trials and the families who supported them; Donna Bucci and the CALGB/Alliance Leukemia Tissue Bank at The Ohio State University Comprehensive Cancer Center, Columbus, OH, for sample processing and storage services and Lisa J. Sterling and Christine Finks for data management. This work was supported in part by the National Cancer Institute (grants CA101140, CA140158, CA180861, CA196171, CA016058, CA180821, CA180882, and CA077658), the Leukemia Clinical Research Foundation, the Warren D. Brown Foundation, the Pelotonia Fellowship Program (to A-KE), and by an allocation of computing resources from The Ohio Supercomputer Center. The content of this article is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

Author contributions

KM, A-KE, and CDB designed the study; KM, A-KE, CJW, MB, JCB, and CDB contributed to the data interpretation, KM, A-KE, JK, and CDB wrote the manuscript; A-KE, CJW, and DP performed laboratory-based research; JSB performed the data processing; JK and DN performed statistical analysis; KM, AJC, ESW, GLU, JEK, BLP, WB, RMS, JCB, and CDB were involved directly or indirectly in the care of patients and/or sample procurement. All authors reviewed the manuscript and approved its final version.

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Author notes

  1. These authors contributed equally: Krzysztof Mrózek, Ann-Kathrin Eisfeld


  1. The Ohio State University Comprehensive Cancer Center, Columbus, OH, USA

    • Krzysztof Mrózek
    • , Ann-Kathrin Eisfeld
    • , Jessica Kohlschmidt
    • , Christopher J. Walker
    • , Deedra Nicolet
    • , Marius Bill
    • , Dimitrios Papaioannou
    •  & Clara D. Bloomfield
  2. Alliance Statistics and Data Center, The Ohio State University Comprehensive Cancer Center, Columbus, OH, USA

    • Jessica Kohlschmidt
    •  & Deedra Nicolet
  3. University of Alabama at Birmingham, Birmingham, AL, USA

    • Andrew J. Carroll
  4. Division of Hematology, Department of Internal Medicine, The Ohio State University Comprehensive Cancer Center, Columbus, OH, USA

    • James S. Blachly
    •  & John C. Byrd
  5. Department of Medicine, Roswell Park Cancer Institute, Buffalo, NY, USA

    • Eunice S. Wang
  6. Washington University School of Medicine in St. Louis, Siteman Cancer Center, St. Louis, MO, USA

    • Geoffrey L. Uy
  7. Monter Cancer Center, Hofstra Northwell School of Medicine, Lake Success, NY, USA

    • Jonathan E. Kolitz
  8. Wake Forest Baptist Comprehensive Cancer Center, Winston-Salem, NC, USA

    • Bayard L. Powell
  9. Emory University School of Medicine, Atlanta, GA, USA

    • William Blum
  10. Dana-Farber/Partners CancerCare, Boston, MA, USA

    • Richard M. Stone


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