Biomaterial Database

Prognostic implication of FLT3 and N-RAS gene mutations in acute myeloid leukemia. 1999

H Kiyoi, and T Naoe, and Y Nakano, and S Yokota, and S Minami, and S Miyawaki, and N Asou, and K Kuriyama, and I Jinnai, and C Shimazaki, and H Akiyama, and K Saito, and H Oh, and T Motoji, and E Omoto, and H Saito, and R Ohno, and R Ueda

Department of Infectious Diseases, Nagoya University School of Medicine, Nagoya, Japan.

Internal tandem duplication of the FLT3 gene and point mutations of the N-RAS gene are the most frequent somatic mutations causing aberrant signal-transduction in acute myeloid leukemia (AML). However, their prognostic importance is unclear. In this study, their prognostic significance was analyzed in 201 newly diagnosed patients with de novo AML except acute promyelocytic leukemia. Three patients had mutations in both genes, 43 had only the FLT3 gene mutation, 25 had only the N-RAS gene mutation, and 130 had neither. These mutations seemed to occur independently. Both mutations were related to high peripheral white blood cell counts, and the FLT3 gene mutation was infrequently observed in the French-American-British (FAB)-M2 type. AML cases with wild FLT3/mutant N-RAS had a lower complete remission (CR) rate than those with wild FLT3/wild N-RAS, whereas the presence of mutant FLT3 did not affect the CR rate. Univariate analysis showed that unfavorable prognostic factors for overall survival were age 60 years or older (P =.0002), cytogenetic data (P =.002), FAB types other than M2 (P =.002), leukocytosis over 100 +/- 10(9)/L (P =.003), and the FLT3 gene mutation (P =.004). However, the N-RAS gene mutation was only a marginal prognostic factor (P =.06). For the subjects under 60 years old, multivariate analysis showed that the FLT3 gene mutation was the strongest prognostic factor (P =.008) for overall survival. The FLT3 gene mutation, whose presence is detectable only by genomic polymerase chain reaction amplification and gel electrophoresis, might serve as an important molecular marker to predict the prognosis of patients with AML.

UI	MeSH Term	Description	Entries
D007951	Leukemia, Myeloid	Form of leukemia characterized by an uncontrolled proliferation of the myeloid lineage and their precursors (MYELOID PROGENITOR CELLS) in the bone marrow and other sites.	Granulocytic Leukemia,Leukemia, Granulocytic,Leukemia, Myelocytic,Leukemia, Myelogenous,Myelocytic Leukemia,Myelogenous Leukemia,Myeloid Leukemia,Leukemia, Monocytic, Chronic,Monocytic Leukemia, Chronic,Chronic Monocytic Leukemia,Chronic Monocytic Leukemias,Granulocytic Leukemias,Leukemia, Chronic Monocytic,Leukemias, Chronic Monocytic,Leukemias, Granulocytic,Leukemias, Myelocytic,Leukemias, Myelogenous,Leukemias, Myeloid,Monocytic Leukemias, Chronic,Myelocytic Leukemias,Myelogenous Leukemias,Myeloid Leukemias
D007958	Leukocyte Count	The number of WHITE BLOOD CELLS per unit volume in venous BLOOD. A differential leukocyte count measures the relative numbers of the different types of white cells.	Blood Cell Count, White,Differential Leukocyte Count,Leukocyte Count, Differential,Leukocyte Number,White Blood Cell Count,Count, Differential Leukocyte,Count, Leukocyte,Counts, Differential Leukocyte,Counts, Leukocyte,Differential Leukocyte Counts,Leukocyte Counts,Leukocyte Counts, Differential,Leukocyte Numbers,Number, Leukocyte,Numbers, Leukocyte
D008297	Male		Males
D008875	Middle Aged	An adult aged 45 - 64 years.	Middle Age
D009154	Mutation	Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations.	Mutations
D011379	Prognosis	A prediction of the probable outcome of a disease based on a individual's condition and the usual course of the disease as seen in similar situations.	Prognostic Factor,Prognostic Factors,Factor, Prognostic,Factors, Prognostic,Prognoses
D011518	Proto-Oncogene Proteins	Products of proto-oncogenes. Normally they do not have oncogenic or transforming properties, but are involved in the regulation or differentiation of cell growth. They often have protein kinase activity.	Cellular Proto-Oncogene Proteins,c-onc Proteins,Proto Oncogene Proteins, Cellular,Proto-Oncogene Products, Cellular,Cellular Proto Oncogene Proteins,Cellular Proto-Oncogene Products,Proto Oncogene Products, Cellular,Proto Oncogene Proteins,Proto-Oncogene Proteins, Cellular,c onc Proteins
D011519	Proto-Oncogenes	Normal cellular genes homologous to viral oncogenes. The products of proto-oncogenes are important regulators of biological processes and appear to be involved in the events that serve to maintain the ordered procession through the cell cycle. Proto-oncogenes have names of the form c-onc.	Proto-Oncogene,Proto Oncogene,Proto Oncogenes
D011905	Genes, ras	Family of retrovirus-associated DNA sequences (ras) originally isolated from Harvey (H-ras, Ha-ras, rasH) and Kirsten (K-ras, Ki-ras, rasK) murine sarcoma viruses. Ras genes are widely conserved among animal species and sequences corresponding to both H-ras and K-ras genes have been detected in human, avian, murine, and non-vertebrate genomes. The closely related N-ras gene has been detected in human neuroblastoma and sarcoma cell lines. All genes of the family have a similar exon-intron structure and each encodes a p21 protein.	Ha-ras Genes,Ki-ras Genes,N-ras Genes,c-Ha-ras Genes,c-Ki-ras Genes,c-N-ras Genes,ras Genes,v-Ha-ras Genes,v-Ki-ras Genes,H-ras Genes,H-ras Oncogenes,Ha-ras Oncogenes,K-ras Genes,K-ras Oncogenes,Ki-ras Oncogenes,N-ras Oncogenes,c-H-ras Genes,c-H-ras Proto-Oncogenes,c-Ha-ras Proto-Oncogenes,c-K-ras Genes,c-K-ras Proto-Oncogenes,c-Ki-ras Proto-Oncogenes,c-N-ras Proto-Oncogenes,ras Oncogene,v-H-ras Genes,v-H-ras Oncogenes,v-Ha-ras Oncogenes,v-K-ras Genes,v-K-ras Oncogenes,v-Ki-ras Oncogenes,Gene, Ha-ras,Gene, Ki-ras,Gene, v-Ha-ras,Gene, v-Ki-ras,Genes, Ha-ras,Genes, Ki-ras,Genes, N-ras,Genes, v-Ha-ras,Genes, v-Ki-ras,H ras Genes,H ras Oncogenes,H-ras Gene,H-ras Oncogene,Ha ras Genes,Ha ras Oncogenes,Ha-ras Gene,Ha-ras Oncogene,K ras Genes,K ras Oncogenes,K-ras Gene,K-ras Oncogene,Ki ras Genes,Ki ras Oncogenes,Ki-ras Gene,Ki-ras Oncogene,N ras Genes,N ras Oncogenes,N-ras Gene,N-ras Oncogene,c H ras Genes,c H ras Proto Oncogenes,c Ha ras Genes,c Ha ras Proto Oncogenes,c K ras Genes,c K ras Proto Oncogenes,c Ki ras Genes,c Ki ras Proto Oncogenes,c N ras Genes,c N ras Proto Oncogenes,c-H-ras Gene,c-H-ras Proto-Oncogene,c-Ha-ras Gene,c-Ha-ras Proto-Oncogene,c-K-ras Gene,c-K-ras Proto-Oncogene,c-Ki-ras Gene,c-Ki-ras Proto-Oncogene,c-N-ras Gene,c-N-ras Proto-Oncogene,ras Gene,ras Oncogenes,v H ras Genes,v H ras Oncogenes,v Ha ras Genes,v Ha ras Oncogenes,v K ras Genes,v K ras Oncogenes,v Ki ras Genes,v Ki ras Oncogenes,v-H-ras Gene,v-H-ras Oncogene,v-Ha-ras Gene,v-Ha-ras Oncogene,v-K-ras Gene,v-K-ras Oncogene,v-Ki-ras Gene,v-Ki-ras Oncogene
D012074	Remission Induction	Therapeutic act or process that initiates a response to a complete or partial remission level.	Induction of Remission,Induction, Remission,Inductions, Remission,Remission Inductions