@article{Allan Beke_Lucie Laplane_Julie Riviere_Qin Yang_Miguel Torres-Martin_Thibault Dayris_Philippe Rameau_Veronique Saada_Chrystèle Bilhou-Nabera_Ana Hurtado_Larissa Lordier_William Vainchenker_Maria E. Figueroa_Nathalie Droin_Eric Solary_2020, place={Pavia, Italy}, title={Multilayer intraclonal heterogeneity in chronic myelomonocytic leukemia}, volume={105}, url={https://haematologica.org/article/view/9481}, DOI={10.3324/haematol.2018.208488}, abstractNote={The functional diversity of cells that compose myeloid malignancies, i.e., the respective roles of genetic and epigenetic heterogeneity in this diversity, remains poorly understood. This question is addressed in chronic myelomonocytic leukemia, a myeloid neoplasm in which clinical diversity contrasts with limited genetic heterogeneity. To generate induced pluripotent stem cell clones, we reprogrammed CD34<sup>+</sup> cells collected from a patient with a chronic myelomonocytic leukemia in which whole exome sequencing of peripheral blood monocyte DNA had identified 12 gene mutations, including a mutation in <em>KDM6A</em> and two heterozygous mutations in <em>TET2</em> in the founding clone and a secondary <em>KRAS</em>(G12D) mutation. CD34<sup>+</sup> cells from an age-matched healthy donor were also reprogrammed. We captured a part of the genetic heterogeneity observed in the patient, i.e. we analyzed five clones with two genetic backgrounds, without and with the <em>KRAS</em&gt;(G12D) mutation. Hematopoietic differentiation of these clones recapitulated the main features of the patient’s disease, including overproduction of granulomonocytes and dysmegakaryopoiesis. These analyses also disclosed significant discrepancies in the behavior of hematopoietic cells derived from induced pluripotent stem cell clones with similar genetic background, correlating with limited epigenetic changes. These analyses suggest that, beyond the coding mutations, several levels of intraclonal heterogeneity may participate in the yet unexplained clinical heterogeneity of the disease.}, number={1}, journal={Haematologica}, author={Allan Beke and Lucie Laplane and Julie Riviere and Qin Yang and Miguel Torres-Martin and Thibault Dayris and Philippe Rameau and Veronique Saada and Chrystèle Bilhou-Nabera and Ana Hurtado and Larissa Lordier and William Vainchenker and Maria E. Figueroa and Nathalie Droin and Eric Solary}, year={2020}, month={Jan.}, pages={112-123} }