Concurrent mutations in two different ras genes in acute myelocytic leukemias.

Oncogenic NRAS, KRAS, and HRAS exhibit different leukemogenic potentials in mice.

RAS proteins are small GTPases that play a central role in transducing signals that regulate cell proliferation, survival, and differentiation. The RAS proteins interact with a common set of activators and effectors; however, they associate with different microdomains of the plasma membrane as well as other endomembranes and are capable of generating distinct signal outputs. Mutations that resu...

Transforming genes in human leukemia cells.

High-molecular weight DNAs of fresh bone marrow cells from 32 patients with fresh leukemia were assayed for the presence of transmissible activated transforming genes by a DNA-mediated gene transfer technique using NIH/3T3 cells. DNAs of bone marrow cells from four of the 32 patients induced transformation of NIH/3T3 cells. Two of the four cases, a chronic myelogenous leukemia and an acute lymp...

N-ras gene point mutations in childhood acute lymphocytic leukemia correlate with a poor prognosis.

Ras genes can be altered by point mutations at critical portions of their coding regions to acquire transforming ability in vitro. These point mutations have been detected in a variety of human malignancies. However, their relevance for the clinical and biologic behavior of the subgroups of patients exhibiting these mutations in unclear. We analyzed 100 patients with childhood acute lymphocytic...

EVI1-rearranged acute myeloid leukemias are characterized by distinct molecular alterations.

The genetic and transcriptional signature of EVI1 (ecotropic viral integration site 1)-rearranged (EVI1-r) acute myeloid leukemias (AMLs) remains poorly defined. We performed RNA sequencing of 12 EVI1-r AMLs and compared the results with those of other AML subtypes (n = 139) and normal CD34(+) cells (n = 17). Results confirm high frequencies of RAS and other activated signaling mutations (10/12...

Identification of novel therapeutic targets in acute leukemias with NRAS mutations using a pharmacological approach