Measurable Residual Disease Monitoring by Locked Nucleic Acid Quantitative Real-Time PCR Assay for Mutation in Adult AML.

Locked nucleic acid quantitative Real-Time PCR (LNA-qPCR) for IDH1/2 mutations in AML measurable residual disease (MRD) detection is rarely reported. LNA-qPCR was applied to quantify IDH1/2 mutants MRD kinetics in bone marrow from 88 IDH1/2-mutated AML patients, and correlated with NPM1-MRD, clinical characteristics, and outcomes. The median normalized copy number (NCN) of IDH1/2 mutants decreased significantly from 53,228 (range 87−980,686)/ALB × 106 at diagnosis to 773 (range 1.

Biological Activities of RUNX1 Mutants Predict Secondary Acute Leukemia Transformation from Chronic Myelomonocytic Leukemia and Myelodysplastic Syndromes.

Purpose: Transcription factor RUNX1 is essential for normal hematopoiesis. High mutation frequencies of RUNX1 gene in chronic myelomonocytic leukemia (CMML) and myelodysplastic syndromes (MDS) have been described, whereas the biologic significances of the mutations were not investigated. Here, we aimed to correlate the biologic activities of the RUNX1 mutants with the clinical outcomes of patients.

Clonal leukemic evolution in myelodysplastic syndromes with TET2 and IDH1/2 mutations.

Somatic mutations of TET2, IDH1, and IDH2 have been described in myelodysplastic syndrome. The impact of these mutations on outcome of myelodysplastic syndrome and their progression to secondary acute myeloid leukemia remains unclear. Mutation status of TET2, IDH1 and IDH2 was investigated in a cohort of 46 paired myelodysplastic syndrome/acute myeloid leukemia samples and 122 non-paired cases with de novo myelodysplastic syndrome, to clarify their roles in the evolution of myelodysplastic syndrome to acute myeloid leukemia.

A high occurrence of acquisition and/or expansion of C-CBL mutant clones in the progression of high-risk myelodysplastic syndrome to acute myeloid leukemia.

The molecular pathogenesis of myelodysplastic syndrome (MDS) and its progression to secondary acute myeloid leukemia (sAML) remain to be explored. Somatic C-CBL mutations were recently described in MDS. Our study aimed to determine the role of C-CBL mutations in the progression of MDS to sAML and sought to correlate with clinicohematological features and outcome.

Heterogeneous patterns of CEBPalpha mutation status in the progression of myelodysplastic syndrome and chronic myelomonocytic leukemia to acute myelogenous leukemia.

Purpose: We aimed to assess the role of CEBPalpha mutations in the progression of myelodysplastic syndrome (MDS) to acute myelogenous leukemia (AML) and their cooperating mutations.

Experimental Design: Mutational analysis of CEBPalpha with direct sequencing for each PCR product was done on matched bone marrow samples obtained from 50 adult patients with MDS at diagnosis and at AML transformation. Cloning analysis was used to determine the allelic distribution.

Internal tandem duplication of fms-like tyrosine kinase 3 is associated with poor outcome in patients with myelodysplastic syndrome.

Background: The prognostic significance of internal tandem duplication (ITD) of the fms-like tyrosine kinase 3 gene (FLT3) for patients with myelodysplastic syndrome (MDS) is not clearly defined. In the current study, the authors sought to assess the value of FLT3/ITD mutation status as a prognostic genetic marker for patients with MDS.

Methods: FLT3/ITD mutation status was evaluated by performing DNA polymerase chain reaction assays on 198 bone marrow samples obtained from patients with MDS at initial diagnosis.

Heterogeneous patterns of FLT3 Asp(835) mutations in relapsed de novo acute myeloid leukemia: a comparative analysis of 120 paired diagnostic and relapse bone marrow samples.

Purpose: We analyzed Asp(835) mutations of FLT3 on paired marrow samples at diagnosis and relapse from 120 adult patients with de novo acute myeloid leukemia (AML) to determine the role of FLT3 Asp(835) mutation in the relapse of AML.

Experimental Design: Asp(835) mutation was analyzed by DNA PCR amplification of exon 20 of FLT3 gene followed by EcoRV digestion. All of the mutations were confirmed by sequence analysis.

Internal tandem duplication and Asp835 mutations of the FMS-like tyrosine kinase 3 (FLT3) gene in acute promyelocytic leukemia.

Background: The clinical relevance of mutations of the FMS-like tyrosine kinase 3 (FLT3) gene in specific cytogenetic subgroups is not clear. The authors examined internal tandem duplication (ITD) and Asp835 mutations of FLT3 in patients with acute promyelocytic leukemia (APL) to determine the incidence of these mutations and to analyze the results for correlations with clinicohematologic features and outcome.

Methods: Bone marrow samples from 107 patients with APL were analyzed.

Farnesyl pyrophosphate promotes and is essential for the binding of RACK1 with beta-tubulin.

Receptors for activated C kinase (RACKs) are a group of protein kinase C (PKC) binding proteins that have been shown to be crucial in the translocation and subsequent functioning of PKC on activation. RACK1 isolated from BALB/3T3 cells transformed with S-ras(Q61K) exhibits receptor activity for PKCgamma as competent as that of RACK1 from BALB/3T3 cells without transformation. However, the ability of RACK1 from transformed cells to bind with beta-tubulin peptide specific for Taxol (PEPtaxol) is defective.

Internal tandem duplication of FLT3 in relapsed acute myeloid leukemia: a comparative analysis of bone marrow samples from 108 adult patients at diagnosis and relapse.

Analysis of internal tandem duplications of FLT3 (FLT3/ITD) was performed on bone marrow samples obtained at diagnosis and relapse from 108 adult patients with de novo acute myeloid leukemia (AML) to determine the role of this mutation in leukemic relapse. Eighty-three patients had wild-type FLT3 at both diagnosis and relapse, 16 had FLT3/ITD at both stages, whereas 8 had acquired the mutation and 1 had lost it at relapse. Using Genescan analysis, we found that FLT3/ITD levels at first relapse were significantly higher than those at diagnosis (mean +/- SE, 40.