OBJECTIVE: To investigate the clinical characteristics of RAS gene mutations in patients with acute myeloid leukemia (AML). METHODS: 43 myeloid gene mutations were detected using next-generation sequencing (NGS) in 180 patients with AML who were first diagnosed between May 2011 and February 2021. The molecular and clinical features of RAS gene mutations and their effects on efficacy and survival of patients were retrospectively analyzed. RESULTS: Among 180 AML patients, the proportion of mutations in RAS pathway-related genes were NRAS (14.4%), KRAS (2.2%), FLT3-ITD (13.8%), PTPN11 (7.7%), KIT (5.0%), FLT3-TKD (3.8%) and CBL (2.7%). Seventy-three (40.6%) AML patients had gene mutations associated with the RAS pathway.The number of peripheral blood white blood cells and the proportion of bone marrow primitive juvenile cells in patients with NRAS/KRAS gene mutation were higher than those of patient with RAS wild-type, the difference was statistically significant (P<0.05). NRAS/KRAS gene mutations were significantly associated with the CBL gene mutation(r=0.287). In young AML patients (age <60 years), there were no significant differences in complete response rate (CR), progression-free survival (PFS), and overall survival (OS) between patients with RAS gene mutation and those with wild-type(P>0.05). In elderly AML patients (age≥60 years), PFS and OS in RAS mutants were significantly lower than those in wild-type patients(P<0.05). CONCLUSION In AML patients, RAS gene mutation is relatively common, and RAS gene mutation is associated with clinical characteristics and efficacy of patients, and may be a molecular marker of poor prognosis for elderly AML.
Aged ; Genes, ras ; Humans ; Leukemia, Myeloid, Acute/genetics* ; Middle Aged ; Mutation ; Nucleophosmin ; Prognosis ; Proto-Oncogene Proteins p21(ras)/genetics* ; Retrospective Studies ; fms-Like Tyrosine Kinase 3/genetics*

OBJECTIVETo explore the pathogenesis of idiopathic thrombocytopenic purpura (ITP) and improve the differential diagnosis from myelodysplastic syndromes (MDS).

METHODSPolymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) was performed to detect the point mutation of codon 12,13 in N-ras gene and codon 301, 969 in fms gene in adult and aged ITP and MDS patients.

RESULTSIn 25 ITP patients, N-ras mutation and fms mutation were detected in one each (4%). Mutations were found in 3 of 8 MDS patients: two (25%) with N-ras mutation and one (12.5%) with fms mutation.

CONCLUSIONSPatients with N-ras or fms gene mutation diagnosed as MDS rather than ITP.

Adult ; Aged ; Female ; Genes, fms ; genetics ; Genes, ras ; genetics ; Humans ; Male ; Middle Aged ; Myelodysplastic Syndromes ; genetics ; Point Mutation ; Polymerase Chain Reaction ; Polymorphism, Single-Stranded Conformational ; Purpura, Thrombocytopenic, Idiopathic ; genetics

OBJECTIVETo study the action mechanism of Yiqi Yangyin Recipe (YYR) in treating leukemia by observing the effects of YYR and its different assembling, energy supporting part (P1) and evil dispelling part (P2) on expressions of Flt3 and N-ras gene in acute myeloid leukemic (AML) cells.

METHODSThe mononuclear cells collected from bone marrow of 60 AML patients were assigned to four groups: the blank was untreated for control and the three tested groups were treated with YYR, P1 and P2, respectively. The effects on Flt3 and N-ras gene expressions and FLT3 protein expression were observed by RT-PCR and Western bloting.

RESULTSRT-PCR test showed the expression of Flt3 in the control, YYR, P1 and P2, group was 90.78% +/- 6.92%, 38.18% +/- 4.50%, 65.57% +/- 5.55% and 61.35% +/- 6.39%, respectively; and that of N-ras in them 93.28% +/- 5.54%, 34.38% +/- 6.69%, 59.42% +/- 7.35% and 65.28% +/- 7.64%, respectively, both showed significant difference as compared the data in the tested groups with those in the control group (P < 0.05). Western bloting test showed the FLT3 protein gray value in the four groups was 0.8127 +/- 0.0284, 0.4265 +/- 0.0353, 0.5396 +/- 0.0274 and 0.5473 +/- 0.0282, respectively, also showed significant difference between the control and the tested groups (P < 0.01).

CONCLUSIONYYR can inhibit the colonic proliferation of AML cells, decrease the expressions of FLT3 and N-ras in cells, therefore shows a therapeutic effect on AML.

Adolescent ; Adult ; Bone Marrow Cells ; pathology ; Child ; Drugs, Chinese Herbal ; pharmacology ; Female ; Genes, ras ; Humans ; Leukemia, Myeloid, Acute ; genetics ; pathology ; Leukocytes, Mononuclear ; metabolism ; pathology ; Male ; Middle Aged ; Tumor Cells, Cultured ; Young Adult ; fms-Like Tyrosine Kinase 3 ; genetics ; metabolism ; ras Proteins ; genetics ; metabolism

This study was aimed to explore whether multiple common gene mutations of leukemia synergistically involved in acute promyelocytic leukemia (APL) pathogenesis, and to investigate their relevance to clinical features, cytogenetics and molecular risk stratification. 84 specimens of admitted de novo APL patients from February 2005 to October 2010 were collected, the gene mutations of bone marrow mononuclear cells and clinical features of mutation-positive patients were analyzed by genomic DNA-PCR. The results indicated that the prevalence of mutations was 60.7% (51/84), in which the mutations with the highest incidence were found as FLT3-ITD, reaching 27.4% (23/84). Next, there were 12 cases WT1 mutation, 9 for FLT3-TKD, 7 for TET2, 5 for N-RAS, 4 for ASXL1, 2 for EZH2 mutation and 1 positive case in MLL-PTD, IDH1 and CBL mutation respectively. No mutation was found in other JAK1, DNMT3, c-Kit, NPM1, IDH2, RUNX1 and JAK2 (V617F) common leukemia-related genes. Combined analysis with clinical data demonstrated that the patients with FLT3-ITD mutation displayed higher white blood cell counts, while the patients with N-RAS mutation showed lower platelet counts. Overall survival of these patients was obviously shorten as compared with patients with wild-type. This difference between mutant and wild-type of all above mentioned cases was statistically significant (P < 0.05). The difference between APL with simple t (15;17) and additional abnormal karyotype was not statistically significant. It is concluded that the FLT3-ITD mutation is recurrent genetic change in APL, and together with N-RAS mutation indicates poor prognosis. Additional abnormal karyotype does not associate with prognosis of APL.
Adolescent ; Adult ; Aged ; Child ; DNA Mutational Analysis ; DNA-Binding Proteins ; genetics ; Enhancer of Zeste Homolog 2 Protein ; Female ; Genes, ras ; Humans ; Leukemia, Promyelocytic, Acute ; genetics ; Male ; Middle Aged ; Mutation ; Nuclear Proteins ; genetics ; Polycomb Repressive Complex 2 ; genetics ; Prognosis ; Proto-Oncogene Proteins ; genetics ; Proto-Oncogene Proteins c-kit ; genetics ; Repressor Proteins ; genetics ; Tandem Repeat Sequences ; Young Adult ; fms-Like Tyrosine Kinase 3 ; genetics