China
Africa
Explore chapters and articles related to this topic
Oncogenes and Cancer
Published in Pimentel Enrique, Oncogenes, 2020
However, the behavior of c-myc, c-mos, and other proto-oncogenes in the mentioned hematologic neoplasms is still poorly understood. High levels of c-mjc-related transcripts are present in a human promyelocytic leukemia cell line (HL60).56 In HL-60 cells an active c-N-ras oncogene coexists with the altered c-myc oncogene and it has been speculated that the presence of the two active proto-oncogenes would be required for the full oncogenic transformation of hematopoietic cells.265 The transcriptional activity of c-myc in uncultured cells from different types of childhood leukemia is usually normal.66,68 No translocation of c-mos occurs in acute myeloblastic leukemia associated with (8;21) translocation and no evidence for c-mos rearrangement was detected in cell lines or fresh cells from several types of human myelomas and lymphoproliferative disorders.266,267 A genetic locus, bcl-2, on chromosome 18q21 was detected in an acute B-cell leukemia cell line from a young patient with t(14;18) translocation.268 The bcl-2 locus was cloned but no known oncogenes were present in the isolated probe.
Antiproliferative Potential of Medicinal Plants—an Evaluation by in Vivo, in Vitro, and in Silico Approaches
Published in V. R. Mohan, A. Doss, P. S. Tresina, Ethnomedicinal Plants with Therapeutic Properties, 2019
Ras is the prototypical member of the Ras (RAt sarcoma) superfamily. Its protein is connected in structure and regulate the cell behavior (Goodsell, 1999). The ras gene family consists three closely related forms of genes which have similar structures and encode for p21ras. These p21ras proteins are known to play a significant role in the regulation of normal signal transduction, with high affinity, it binds guanidine triphosphates and possess GTPase, a process that is necessary to shift the ras proteins to an inactive state. The k-ras gene encodes membrane-bound protein involved in the regulation of a number of important normal cellular functions including proliferation, differentiation, and apoptosis. Both the active fractions I and II of B. variegata decreased the expression of k-ras in a dose-dependent manner. The active fractions of B. variegata has also downregulated the TGF-β gene and protein expression. Bcl2 is a human proto-oncogene located on chromosome 18 which is the main regulator of cell death program. Its product is an integral membrane protein which is located in the membranes of the endoplasmic reticulum, nuclear envelope, and in the outer membranes of mitochondria. Bcl2 was discovered in B-cell leukemia at the translocated locus (Yi et al., 2005). Overexpression of Bcl2 is effective in inhibiting cell death thereby apoptosis process is controlled in various cell types (Delbridge and Strasser, 2015).
Human Herpesvirus Type 8/Kaposi Sarcoma Herpesvirus
Published in Satya Prakash Gupta, Cancer-Causing Viruses and Their Inhibitors, 2014
Hiba El Hajj, Raghida Abou Merhi, Ali Bazarbachi
This is a viral lytic protein encoded by ORF-16 and expressed in both spindle cells and monocytes in KS lesions. It only displays 15–20% amino acid identity to cellular B cell leukemia (Bcl-2) but contains the critical BH1 and BH2 domains required to heterodimerize with cellular Bcl-2 and potently suppresses caspase 3 death effector functions (Sarid et al. 1997). It plays a role in inhibiting apoptosis of virally infected cells (Table 10.2) (Friborg et al. 1998). Indeed, the viral analog of B cell leukemia-2 (vBcl-2) prevents apoptosis induced by v-cyclin.
PPARG, GNG12, and CD19 are potential independent predictors of central nerve recurrence in childhood acute lymphoblastic leukemia
Published in Hematology, 2023
Shan Zhang, Yansong Tu, Hurong Lai, Huijun Chen, Huaijun Tu, Jian Li
Studies have reported that sex, hepatomegaly, central nervous system status and age [6–8], neuronal-glial antigen-2 (NG2) expression [9], and CNS microenvironment [10] are all associated with CNS relapse of childhood ALL. Another study showed that the up-regulation of the PBx1 gene in B-cell leukemia in mouse CNS microenvironment could enhance the chemotherapy-resistance and self-renewal characteristics of leukemia cells [11]. Organomegaly at diagnosis was a highly significant clinical predictor for relapse [12]. In addition, acute leukemia patients with CNSL, which showed positive CD19 expression in tumor cell immunotyping and remission after anti-CD19 CAR T cell therapy [13]. It could also be a potential predictor. However, as these studies were based only on clinical data or animal experiments, there is still no independent predictor and lack of a corresponding prediction model for CNS relapse in childhood ALL.
Immunologic evaluation and genetic defects of apoptosis in patients with autoimmune lymphoproliferative syndrome (ALPS)
Published in Critical Reviews in Clinical Laboratory Sciences, 2021
Laura Casamayor-Polo, Marta López-Nevado, Estela Paz-Artal, Alberto Anel, Frederic Rieux-Laucat, Luis M. Allende
Apoptosis is induced by two principal pathways, the intrinsic or mitochondrial pathway and the extrinsic or death receptor pathway. The intrinsic or mitochondrial pathway is triggered by irradiation, growth factor withdrawal or chemotherapeutic agents. It is controlled by the balance of B cell leukemia-2 (Bcl-2) family members, which consist of pro-apoptotic (Bim, Bax, Bak, Puma, Noxa, Bad, Bcl-Xs, Bid, Bik) and anti-apoptotic (Bcl-2, Mcl-1, A1, Bcl-XL, Bcl-W) members [15]. Once these downstream pro-apoptotic members are activated, the mitochondrial membrane potential is disrupted, which results in the release of cytochrome C and a second mitochondrial activator of caspases from the mitochondrial intermembrane space into the cytoplasm. Newly released cytochrome C, along with dATP, binds adaptor protein apoptotic protease-activating factor 1; this in turn leads to the formation of the apoptosome complex that recruits and activates initiator caspase 9. Activated caspase 9 then activates effector caspases 3 and 7, leading to the cleavage of protein substrates and cell death [16].
The efficacy and adverse events of venetoclax in combination with hypomethylating agents treatment for patients with acute myeloid leukemia and myelodysplastic syndrome: a systematic review and meta-analysis
Published in Hematology, 2020
Yuancheng Guo, Bei Liu, Lijuan Deng, Yanhong Qiao, Jinli Jian
The antiapoptotic protein B-cell leukemia/lymphoma-2(BCL-2) is overexpressed in hematologic malignancies and is associated with maintenance and survival of AML cells, treatment resistance and poor overall survival in AML patients. In addition, abnormal overexpression of BCL-2 has been found in patients with high-risk MDS. VEN is an oral, potent BCL-2 inhibitor that causes rapid tumour cell apoptosis by specifically inhibiting the Bcl-2 protein and activating the endogenous mitochondrial apoptotic pathway [3]. Recent clinical data have shown that VEN in combination with HMAs has a CR/CR with imcomplete recovery of peripheral blood counts(CRi) rate of 67% in ND-AML patients over 65 years of age who are not candidates for intensive therapy [4], and the Food and Drug Administration(FDA) granted accelerated approval to VEN in combination with HMAs for the treatment of ND-AML in adults who are aged 75 years or older, or who have comorbidities that preclude use of intensive induction chemotherapy. Related preclinical studies also have shown The addition of VEN to AZA may benefit patients with high-risk MDS [5]. However, most of the published studies are generally small in scale, so evidence for these study results remains relatively limited.