IDH1 and IDH2 mutations confer an adverse effect in patients with acute myeloid leukemia lacking the NPM1 mutation.

We examined the incidence and prognostic effect of IDH1 and IDH2 mutations in 233 Japanese adults with acute myeloid leukemia (AML). IDH1 R132 mutations were detected in 20 (8.6%) patients with AML.

High frequency of IKZF1 genetic alterations in adult patients with B-cell acute lymphoblastic leukemia.

Alterations in the IKZF1 gene are associated with poor prognosis in pediatric B-cell acute lymphoblastic leukemia (B-ALL). We examined the relationship between IKZF1 alterations and clinical findings in 78 adult patients with B-ALL. Aberrant isoforms of IKZF1 were detected using RT-PCR.

Mutation in the RNA binding protein TIS11D/ZFP36L2 is associated with the pathogenesis of acute leukemia.

TIS11D is an AU-rich element binding protein that is involved in RNA metabolism and definitive hematopoiesis. Although disruption of genes related to hematopoiesis often leads to the development of leukemia and lymphoma, the involvement of TIS11D in hematological malignancies remains to be determined. In the present study, we identified a heterozygous frameshift mutation (I373fsX91) in the carboxy-terminus of the TIS11D gene in leukemic cells from a patient with acute myeloid leukemia.

A family harboring a germ-line N-terminal C/EBPalpha mutation and development of acute myeloid leukemia with an additional somatic C-terminal C/EBPalpha mutation.

C/EBPalpha plays an essential role as a transcription factor in myeloid cell differentiation. Here, we describe a Japanese family in which two individuals with acute myeloid leukemia (AML) and one healthy individual had an identical 4-base pair insertion in the N-terminal region of CEBPA (350_351insCTAC), resulting in the termination at codon 107 (I68fsX107). The father and a son at diagnosis of AML had different in-frame insertion mutations in the C-terminal region of C/EBPalpha.

p15 mRNA expression detected by real-time quantitative reverse transcriptase-polymerase chain reaction correlates with the methylation density of the gene in adult acute leukemia.

Cyclin-dependent kinase inhibitor p15 is frequently inactivated by either methylation or deletion in patients with acute leukemia. To examine pathologic and clinical significance of the p15 gene inactivation, we established a quantitative assay of p15 mRNA expression in the bone marrow cells by real-time quantitative reverse transcriptase-polymerase chain reaction. p15 mRNA expression in 14 patients with precursor B-cell acute lymphoblastic leukemia (PBC-ALL) well correlated with status of deletion and methylation in the p15 gene analyzed by Southern blotting.