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RESEARCH PRODUCT
Prognostic value of FLT3 mutations in patients with acute promyelocytic leukemia treated with all-trans retinoic acid and anthracycline monochemotherapy
María José LarrayozMiguel A. SanzPedro Sánchez-godoyEva BarragánMaría Teresa Gómez-casaresDolors ColomerCarmen ChillónBob LöwenbergMarcos GonzálezMaría José CalasanzMireia CamósJose Roman-gomezJavier María García LópezJosé González-camposEdo VellengaOscar FusterFélix MansoPau MontesinosRosa AyalaMaria L. Amadorsubject
MaleAIDA PROTOCOLGene mutationmedicine.disease_causeGastroenterologyLeukemia Promyelocytic AcuteRESIDUAL DISEASEhemic and lymphatic diseasesMOLECULAR SUBTYPESChildanthracyclinesMutationRemission InductionFLT3 mutationshemic and immune systemsHematologyMiddle AgedPrognosisall-trans retinoic acidLeukemiaTreatment Outcomeembryonic structuresFemaleTandem exon duplicationmedicine.drugAcute promyelocytic leukemiaAdultmedicine.medical_specialtyAdolescentAntineoplastic AgentsTretinoinACUTE MYELOID-LEUKEMIABiologyYoung AdultQUALITY-CONTROLTretinoinPOOR-PROGNOSISInternal medicinemedicineCoagulopathyHumansAgedprognostic factorsOriginal Articlesacute promyelocytic leukemiamedicine.diseaseSurvival AnalysisINTERNAL TANDEM DUPLICATIONRISK-ADAPTED TREATMENTPML/RAR-ALPHAfms-Like Tyrosine Kinase 3Fms-Like Tyrosine Kinase 3ImmunologyPETHEMA GROUPMutationdescription
Background Fms-like tyrosine kinase-3 (FLT3) gene mutations are frequent in acute promyelocytic leukemia but their prognostic value is not well established. Design and Methods We evaluated FLT3-internal tandem duplication and FLT3-D835 mutations in patients treated with all-trans retinoic acid and anthracycline-based chemotherapy enrolled in two subsequent trials of the Programa de Estudio y Tratamiento de las Hemopatias Malignas (PETHEMA) and Hemato-Oncologie voor Volwassenen Nederland (HOVON) groups between 1996 and 2005. Results FLT3-internal tandem duplication and FLT3-D835 mutation status was available for 306 (41%) and 213 (29%) patients, respectively. Sixty-eight (22%) and 20 (9%) patients had internal tandem duplication and D835 mutations, respectively. Internal tandem duplication was correlated with higher white blood cell and blast counts, lactate dehydrogenase, relapse-risk score, fever, hemorrhage, coagulopathy, BCR3 isoform, M3 variant subtype, and expression of CD2, CD34, human leukocyte antigen-DR, and CD11b surface antigens. The FLT3-D835 mutation was not significantly associated with any clinical or biological characteristic. Univariate analysis showed higher relapse and lower survival rates in patients with a FLT3-internal tandem duplication, while no impact was observed in relation to FLT3-D835. The prognostic value of the FLT3-internal tandem duplication was not retained in the multivariate analysis. Conclusions FLT3-internal tandem duplication mutations are associated with several hematologic features in acute promyelocytic leukemia, in particular with high white blood cell counts, but we were unable to demonstrate an independent prognostic value in patients with acute promyelocytic leukemia treated with all-trans retinoic acid and anthracycline-based regimens.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2011-10-01 |