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MYELODYSPLASTIC NEOPLASM

Multi-hit TET2 mutations as a differential molecular signature of oligomonocytic and overt chronic myelomonocytic leukemia

Leukemia volume 36, pages 2922–2926 (2022)Cite this article

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Oligomonocytic chronic myelomonocytic leukemia (OM-CMML) is defined as those myelodysplastic neoplasms (MDS) or MDS/MPN unclassifiable cases with relative monocytosis (≥10% monocytes) and a total monocyte count of 0.5 to  ≤ 1 × 109/L [1, 2]. These patients show similar clinical, genomic and immunophenotypic features than overt chronic myelomonocytic leukemia (CMML) [3], although the majority of them are classified as MDS following WHO 2017 classification [4]. Consequently, the upcoming WHO 2022 [5] and International Consensus Classification (ICC) 2022 [6] have lowered the cutoff for absolute monocytosis to 0.5 × 109/L for establishing CMML diagnosis and all those cases meeting OM-CMML criteria will be included into CMML definition. Therefore, the identification of new biological clues supporting this change is of special interest in this scenario.

TET2 is the most prevalent mutated gene in CMML and, unlike other genes, multiple TET2 mutations are frequently found in the same patient at diagnosis [3, 7,8,9]. Previous studies in large cohorts of myeloid neoplasms described the association of biallelic TET2 mutations to monocytosis, CMML diagnosis and lower-risk disease [10]. Furthermore, early clonal dominance of TET2 has been described as a unique finding in CMML [7]. We hypothesized that the identification of multiple TET2 mutations could be a molecular signature of CMML as reliable as the widely accepted TET2 and SRSF2 co-mutation [11].

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Fig. 1: Characteristics and distribution of TET2 mutations.

Data availability

Data available on request from the corresponding author

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Acknowledgements

This study was supported in part by grants from ISCIII-FEDER FIS PI16/0153, FIS PI17/313, FIS PI19/0005, 2017SGR205, and 2017SGR437, PT20/00023; and Xarxa de Banc de Tumors de Catalunya.

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Authors and Affiliations

  1. Group of Applied Clinical Research in Hematology, IMIM-Hospital del Mar, Barcelona, Spain

    Nieves Garcia-Gisbert, Concepción Fernández-Rodríguez, Sara Garcia-Avila, Patricia Velez, Joan Gibert, Lierni Fernández-Ibarrondo, Antonio Salar & Beatriz Bellosillo

  2. Pompeu Fabra University, Barcelona, Spain

    Nieves Garcia-Gisbert, Lierni Fernández-Ibarrondo & Beatriz Bellosillo

  3. Group of Translational Research on Hematological Neoplasms, IMIM-Hospital del Mar, Barcelona, Spain

    Leonor Arenillas, David Roman-Bravo, Lourdes Florensa, Ana Ferrer & Xavier Calvo

  4. Laboratori de Citologia Hematològica, Department of Pathology, Hospital del Mar, Barcelona, Spain

    Leonor Arenillas, David Roman-Bravo, Lourdes Florensa, Ana Ferrer & Xavier Calvo

  5. Department of Hematology, Hospital del Mar, Barcelona, Spain

    Juan Jose Rodriguez-Sevilla, Sara Garcia-Avila, Patricia Velez & Antonio Salar

  6. Laboratory of Molecular Diagnostics, Pathology Department, Hospital del Mar, Barcelona, Spain

    Concepción Fernández-Rodríguez, Joan Gibert & Beatriz Bellosillo

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  1. Nieves Garcia-Gisbert
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Contributions

NGG performed the research, analyzed and interpreted the results and wrote the manuscript. XC designed the research study, performed the research, analyzed and interpreted the results and wrote the manuscript. LA and DR performed the research, collected the data and interpreted the results. JJRS, CFR, SGA, PV, LFI, AS, LF, BB and AF collected the data and interpreted the results. JG analyzed the data and interpreted the results. All authors reviewed and approved the final version of the manuscript.

Corresponding author

Correspondence to Xavier Calvo.

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Competing interests

BB: Thermo Fisher Scientific (Research Funding, Consultancy, Speakers Bureau), Qiagen (Consultancy, Speakers Bureau), Roche (Research Funding, Speakers Bureau). AS: Roche (Research Funding, Speakers Bureau), Janssen Pharmaceuticals (Consultancy, Speakers Bureau), Gilead (Consultancy, Speakers Bureau), Celgene (Consultancy).

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Garcia-Gisbert, N., Arenillas, L., Roman-Bravo, D. et al. Multi-hit TET2 mutations as a differential molecular signature of oligomonocytic and overt chronic myelomonocytic leukemia. Leukemia 36, 2922–2926 (2022). https://doi.org/10.1038/s41375-022-01733-8

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