The role of minor subpopulations within the leukemic blast compartment of AML patients at initial diagnosis in the development of relapse

C. Bachas, G. J. Schuurhuis, Y. G. Assaraf, Z. J. Kwidama, A. Kelder, F. Wouters, A. N. Snel, G. J.L. Kaspers, J. Cloos

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78 Citaten (Scopus)

Samenvatting

The majority of pediatric and younger adult (60 years) AML patients achieve complete remission. However, 30-40% of patients relapse and display a dismal outcome. Recently we described a frequent instability of type I/II mutations between diagnosis and relapse. Here, we explored the hypothesis that these mutational shifts originate from clonal selection during treatment/disease progression. Subfractions of blasts from initial diagnosis samples were cell sorted and their mutational profiles were compared with those of the corresponding relapse samples of 7 CD34+ AML patients. At diagnosis, subfractions of the CD45dim CD34+ CD38dim/- compartment were heterogeneous in the distribution of mutations, when compared to the whole CD45dim CD34+ blast compartment in 6 out of 7 patients. Moreover, within CD45dim CD34+ CD38 dim/- fraction of initial samples of 5 of these 6 AML patients, we found evidence for the presence of a minor, initially undetected subpopulation with a specific mutational profile that dominated the bulk of leukemic blasts at relapse. In conclusion, our findings lend support to the AML oligoclonality concept and provide molecular evidence for selection and expansion of a chemo-resistant subpopulation towards development of relapse. These results imply that early detection of pre-existing drug-resistant leukemic subpopulations is crucial for relapse prevention by proper timing of targeted treatment.

Originele taal-2Engels
Pagina's (van-tot)1313-1320
Aantal pagina's8
TijdschriftLeukemia
Volume26
Nummer van het tijdschrift6
DOI's
StatusGepubliceerd - jun. 2012
Extern gepubliceerdJa

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