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t(11;16)(q23;p13)/KMT2A-CREBBP in hematologic malignancies: presumptive evidence of myelodysplasia or therapy-related neoplasm?

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Abstract

Fusion partners of KMT2A affect disease phenotype and influence the current World Health Organization classification of hematologic neoplasms. The t(11;16)(q23;p13)/KMT2A-CREBBP is considered presumptive evidence of a myelodysplastic syndrome (MDS) and a MDS-related cytogenetic abnormality in the classification of acute myeloid leukemia (AML). Here, we report 18 cases of hematologic neoplasms with t(11;16). There were 8 males and 10 females with a median age of 51.9 years at time of detection of t(11;16). Of 17 patients with enough clinical information and pathological materials for review, 16 had a history of cytotoxic therapies for various malignancies including 12/15 patients who received topoisomerase II inhibitors, and 15 were classified as having therapy-related neoplasms. The median interval from the diagnosis of primary malignancy to the detection of t(11;16) was 23.2 months. Dysplasia, usually mild, was observed in 7/17 patients. Blasts demonstrated monocytic differentiation in 8/8 patients who developed AML at the time or following detection of t(11;16). t(11;16) was observed as the sole chromosomal abnormality in 10/18 patients. KMT2A rearrangement was confirmed in 11/11 patients. The median survival from the detection of t(11;16) was 15.4 months. In summary, t(11;16)(q23;p13) is rare and overwhelmingly associated with prior exposure of cytotoxic therapy. Instead of being considered presumptive evidence of myelodysplasia, we suggest that the detection of t(11;16) should automatically prompt a search for a history of malignancy and cytotoxic therapy so that proper risk stratification and clinical management are made accordingly. The dismal outcome of patients with t(11;16) is in keeping with that of therapy-related neoplasms.

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Authors and Affiliations

  1. Department of Hematopathology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd., Unit 0072, Houston, TX, 77030, USA

    Wei Xie, Guiling Tang, Sanam Loghavi, Aileen Y. Hu, Sa Wang, Carlos E. Bueso-Ramos, L. Jeffrey Medeiros & Shimin Hu

  2. Department of Pathology, Duke University Medical Center, Durham, NC, USA

    Endi Wang

  3. Department of Pathology, City of Hope National Medical Center, Duarte, CA, USA

    Young Kim & Adam Cloe

  4. Department of Pathology, Florida Hospital, Orlando, FL, USA

    Qi Shen

  5. Department of Laboratory Medicine, University of Washington, Seattle, WA, USA

    Yi Zhou

  6. Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

    Guillermo Garcia-Manero & Hagop M. Kantarjian

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  1. Wei Xie
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Xie, W., Tang, G., Wang, E. et al. t(11;16)(q23;p13)/KMT2A-CREBBP in hematologic malignancies: presumptive evidence of myelodysplasia or therapy-related neoplasm?. Ann Hematol 99, 487–500 (2020). https://doi.org/10.1007/s00277-020-03909-7

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