Structurally distinct ligand-binding or ligand-independent Notch1 mutants are leukemogenic but affect thymocyte development, apoptosis, and metastasis differently.
Using gene expression profiling and chromatin immunoprecipitation, we identified c-myc as a novel, direct, and critical Notch1 target gene in T-cell leukemia. c-myc mRNA levels are increased in primary mouse T-cell tumors that harbor Notch1 mutations, and Notch1 inhibition decreases c-myc mRNA levels and inhibits leukemic cell growth.
Recently, two X-SCID patients treated by gene therapy to rescue T-cell lymphopoiesis developed T-cell leukemias with retroviral insertion into the LMO2 gene causing clonal T-cell proliferation.
One of these, designated Rhom-2, is located on human chromosome 11 at band 11p13, where a cluster of T-cell leukemia-specific translocations occur; all translocation breakpoints at 11p13 are upstream of the Rhom-2 gene.
One of these, designated Rhom-2, is located on human chromosome 11 at band 11p13, where a cluster of T-cell leukemia-specific translocations occur; all translocation breakpoints at 11p13 are upstream of the Rhom-2 gene.
Mutated STAT3 is mainly associated with large granular lymphocytic T-cell leukemia, whereas mutated STAT5B is associated with T-cell prolymphocytic leukemia, T-cell acute lymphoblastic leukemia and γδ T-cell-derived lymphomas.
In addition, the STAT3 inhibitor S3I-201 not only induced cell growth arrest and cell death but also activated caspase-3 in MT-2 and HUT-102 cells, indicating that STAT3 may be a therapeutic target for ATL.
To further examine the cause of this signaling pathway deregulation, we measured mRNA and protein expression levels by real-time PCR and Western blots, respectively, of four negative regulators of the IL-2R signaling pathway including src homology 2 (SH2)-containing phosphatase (SHP1), cytokine-inducible (CIS) SH2-containing protein, suppressor of cytokine signaling-1 (SOCS1) and protein inhibitor of activated signal transducer and activator of transcription 3 (STAT3) (PIAS3) in six HTLV-1 negative and seven HTLV-1 positive T-cell leukemia lines.
The rhombotin family of cysteine-rich LIM-domain oncogenes: distinct members are involved in T-cell translocations to human chromosomes 11p15 and 11p13.
The mechanism of chromosomal translocation t(11;14) involving the T-cell receptor C delta locus on human chromosome 14q11 and a transcribed region of chromosome 11p15.
This is important because it provides a better understanding of the function and role of HBZ in downregulating viral transcription and, hence, its contribution to viral latency and persistence <i>in vivo</i>, a process that may ultimately lead to the development of ATL.
Murine ATL models include transgenic animals for the viral proteins Tax and HBZ, knock-outs for key cellular regulators, xenografts and humanized immune-deficient mice.
Studies suggest that IDH in children may be a marker for the development of T-cell leukemia/lymphoma (ATL) or myelopathy associated with HTLV-1/tropical spastic paraparesis (HAM / TSP) in adulthood.
Adult T-cell leukemia (ATL) and HTLV-1-associated Myelopathy/Tropical Spastic Paraparesis (HAM/TSP) are the two main diseases that are caused by the HTLV-1 virus.
Importantly, we revealed that HTLV-1 bZIP factor (HBZ) protein which is expressed in all ATL cases physically interacts with NRF-1 and inhibits the DNA-binding ability of NRF-1.
Studies suggest that IDH in children may be a marker for the development of T-cell leukemia/lymphoma (ATL) or myelopathy associated with HTLV-1/tropical spastic paraparesis (HAM / TSP) in adulthood.