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Bone Marrow Clonogenic Myeloid Progenitors from NPM1-Mutated AML Patients Do Not Harbor the NPM1 Mutation: Implication for the Cell-Of-Origin of NPM1+ AML

Abstract: The cell-of-origin of NPM1- and FLT3-mutated acute myeloid leukemia (AML) is still a matter of debate. Here, we combined in vitro clonogenic assays with targeted sequencing to gain further insights into the cell-of-origin of NPM1 and FLT3-ITD-mutated AML in diagnostic bone marrow (BM) from nine NPM1+/FLT3-ITD (+/-) AMLs. We reasoned that individually plucked colony forming units (CFUs) are clonal and reflect the progeny of a single stem/progenitor cell. NPM1 and FLT3-ITD mutations seen in the diagnostic blasts were found in only 2/95 and 1/57 individually plucked CFUs, suggesting that BM clonogenic myeloid progenitors in NPM1-mutated and NPM1/FLT3-ITD-mutated AML patients do not harbor such molecular lesions. This supports previous studies on NPM1 mutations as secondary mutations in AML, likely acquired in an expanded pool of committed myeloid progenitors, perhaps CD34-, in line with the CD34-/low phenotype of NPM1-mutated AMLs. This study has important implications on the cell-of-origin of NPM1+ AML, and reinforces that therapeutic targeting of either NPM1 or FLT3-ITD mutations might only have a transient clinical benefit in debulking the leukemia, but is unlikely to be curative since will not target the AML-initiating/preleukemic cells. The absence of NPM1 and FLT3-ITD mutations in normal clonogenic myeloid progenitors is in line with their absence in clonal hematopoiesis of indeterminate potential.

Otras publicaciones de la misma revista o congreso con autores/as de la Universidad de Cantabria

 Fuente: Genes (Basel) . 2020 Jan 9;11(1):73

Editorial: MDPI

 Fecha de publicación: 09/01/2020

Nº de páginas: 5

Tipo de publicación: Artículo de Revista

 DOI: doi: 10.3390/genes11010073

ISSN: 2073-4425

 Proyecto español: SAF2016-80481-R

Url de la publicación: https://doi.org/10.3390/genes11010073

Autoría

DIAZ DE LA GUARDIA, RAFAEL

LAURA GONZALEZ SILVA

LÓPEZ MILLÁN, BELÉN

RODRÍGUEZ SEVILLA, JUAN JOSÉ

BARONI, MATTEO L.

BUENO, CLARA

ANGUITA, EDUARDO

VIVES, SUSANA

PALOMO, LAURA

LAPILLONNE, HELENE

MENÉNDEZ, PABLO