Moreover, hyper-activation of the PI3K-AKT pathway by overexpression of a constitutively active version of AKT (myrAKT) or knockdown of PTEN repressed the growth of BL cell lines.
Patients demonstrating a terminal deoxynucleotidyl transferase (TdT)-positive precursor B cell phenotype with IGH-MYC rearrangement have been reported to be molecularly distinct from BL and closer to B-ALL/LBL.
Moreover, hyper-activation of the PI3K-AKT pathway by overexpression of a constitutively active version of AKT (myrAKT) or knockdown of PTEN repressed the growth of BL cell lines.
Paradoxically, PI3K-AKT activation facilitates MYC-driven lymphomagenesis in mice, and it has been proposed that PI3K-AKT activation is essential for BL.
Patients demonstrating a terminal deoxynucleotidyl transferase (TdT)-positive precursor B cell phenotype with IGH-MYC rearrangement have been reported to be molecularly distinct from BL and closer to B-ALL/LBL.
A subset of HGBCL, NOS displayed recurrent alterations of Burkitt lymphoma related genes such as MYC, ID3 and DDX3X and homozygous deletions of 9p21/CDKN2A whereas other cases were genetically closer to GCB-DLBCL.
Moreover, hyper-activation of the PI3K-AKT pathway by overexpression of a constitutively active version of AKT (myrAKT) or knockdown of PTEN repressed the growth of BL cell lines.
Moreover, hyper-activation of the PI3K-AKT pathway by overexpression of a constitutively active version of AKT (myrAKT) or knockdown of PTEN repressed the growth of BL cell lines.
Our analysis provided a novel look on the transition range between FL and DLBCL, on DLBCL with poor prognosis showing expression patterns resembling that of Burkitt's lymphoma and particularly on 'double-hit' MYC and BCL2 transformed lymphomas.
Thus, the capacity of Tat to spontaneously penetrate B-cells could be sufficient to favor the occurrence of MYC-IGH oncogenic rearrangements during erroneous repair, a plausible cause for the increased incidence of Burkitt lymphoma in the HIV-infected population.
Our analysis provided a novel look on the transition range between FL and DLBCL, on DLBCL with poor prognosis showing expression patterns resembling that of Burkitt's lymphoma and particularly on 'double-hit' MYC and BCL2 transformed lymphomas.
The phosphatidylinositol 3-kinase (PI3K)/RAC-α serine/threonine-protein kinase (AKT) pathway is constitutively activated in a number of lymphoid malignancy types, including diffuse large B-cell lymphoma (DLBCL) and Burkitt lymphoma.
Thus, the capacity of Tat to spontaneously penetrate B-cells could be sufficient to favor the occurrence of MYC-IGH oncogenic rearrangements during erroneous repair, a plausible cause for the increased incidence of Burkitt lymphoma in the HIV-infected population.
However, ectopic IRF4 expression can augment EBV lytic gene expression induced by anti-immunoglobulin (anti-Ig) or sodium butyrate treatment in all tested lymphoma cells, whereas IRF4 knockout in Raji cells, the only BL cell line with detectable endogenous IRF4 expression, abolishes EBV lytic gene expression induced by anti-Ig, and this is accompanied by the reduction of Blimp-1 expression, whose overexpression, in turn, can rescue EBV lytic gene expression in IRF4 knockout Raji cells.
Although sporadic and immunodeficiency-associated BLs had similar genetic profiles, endemic BLs manifested more frequent mutations in BCL7A and BCL6 and fewer genetic alterations in DNMT1, SNTB2, and CTCF.
In addition, the tumour sample of the patient was positive for the classical somatic chromosomal translocation t(8;14) involving the c-MYC gene frequently identified in BL.
The novel mutation patterns identified here imply rational use of DNA-damaging chemotherapy in some patients with BL and targeted agents such as the CDK4/6 inhibitor palbociclib in others, whereas the importance of BCR signaling in BL strengthens the potential benefit of inhibitors for PI3K, Syk, and Src family kinases among these patients.
The novel mutation patterns identified here imply rational use of DNA-damaging chemotherapy in some patients with BL and targeted agents such as the CDK4/6 inhibitor palbociclib in others, whereas the importance of BCR signaling in BL strengthens the potential benefit of inhibitors for PI3K, Syk, and Src family kinases among these patients.
To explore whether disruption of the MYC-WDR5 interaction could potentially become a viable anticancer strategy, we developed a Burkitt's lymphoma system that allows replacement of wild-type MYC for mutants that are defective for WDR5 binding or all known nuclear MYC functions.
The treatment of BL cells with decitabine reduced methylation, induced miR‑29s expression and downregulated MYC protein levels in a dose‑dependent manner.
The phosphatidylinositol 3-kinase (PI3K)/RAC-α serine/threonine-protein kinase (AKT) pathway is constitutively activated in a number of lymphoid malignancy types, including diffuse large B-cell lymphoma (DLBCL) and Burkitt lymphoma.
The novel mutation patterns identified here imply rational use of DNA-damaging chemotherapy in some patients with BL and targeted agents such as the CDK4/6 inhibitor palbociclib in others, whereas the importance of BCR signaling in BL strengthens the potential benefit of inhibitors for PI3K, Syk, and Src family kinases among these patients.