Stem cell mutations can be detected in myeloma patients years before onset of secondary leukemias.
Blood Adv
; 3(23): 3962-3967, 2019 12 10.
Article
en En
| MEDLINE
| ID: mdl-31805192
ABSTRACT
Therapy-related acute myeloid leukemia and myelodysplastic syndromes (t-AML/t-MDS) are secondary hematologic malignancies associated with poor prognosis, warranting insights into their predisposing conditions and cells of origin. We identified patients with myeloma who developed t-AML/t-MDS and analyzed their stem and progenitor cells collected years before the onset of secondary disease. We demonstrate that aberrant stem cells with high CD123 expression can be detected long before the onset of overt leukemia. Rigorous sorting, followed by targeted sequencing, resulted in ultradeep functional depth of sequencing and revealed preexisting mutant hematopoietic stem cell (HSC) clones, mainly harboring TP53 mutations, that became the dominant population at the time of leukemic presentation. Taken together, these data show that HSCs can act as reservoirs for leukemia-initiating cells many years before the onset of myeloid leukemia.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Células Madre Hematopoyéticas
/
Leucemia Mieloide Aguda
/
Neoplasias Primarias Secundarias
/
Mieloma Múltiple
Límite:
Humans
Idioma:
En
Revista:
Blood Adv
Año:
2019
Tipo del documento:
Article