Additional factors may modulate the biological effect of the double hit lesions because tumors in which MYC is translocated to non-IGH partner or MYC and BCL2 protein that are expressed at lower levels may have a less aggressive behavior.
In conclusion, the majority of Bcl-2-negative FL lack a t(14;18) but a significant subset of these tumours are false negative due to mutations in the BCL2 gene.
To clarify the prevalence of BCL6 and BCL2 rearrangements in FL and diffuse large B-cell lymphomas (DLBLs), we performed a large scale bicolor interphase cytogenetic (fluorescence in situ hybridization) study on 188 well-characterized B-NHLs classified according to the World Health Organization Classification of Tumors of the Lymphoid Tissues.
Reconstitution of the p53 gene inhibits cellular growth, and this growth-suppressive effect is partly due to apoptosis involving bcl-2 gene suppression in this tumor type.
Studies of tumor suppressor genes and proto-oncogenes in the BCL2 family genes may unravel the mechanisms of leukemia cell progression and the development of drug resistance, leading to innovative therapies.
Unexpectedly, dissimilar immunoglobulin light and heavy chain gene rearrangements were detected in the paired samples from one patient with previously diagnosed follicular lymphoma, making the relationship of the two tumors from this patient uncertain; however, additional Southern blot analysis of the bcl-2 gene showed identical rearrangements in both lesions.
However, the normal cell apoptotic fractions were higher for the tumors with t(14;18) compared to the tumors without BCL2 alterations, while the tumors with gain of BCL2 only showed intermediate levels.
Patients with glomangiopericytoma had a tendency toward longer overall survival when they were diagnosed at a younger age (≤60 years; P = .001), did not demonstrate marginal involvement (P = .032), recurrence/metastasis (P = .002), or radiotherapy/chemotherapy (P = .010), and had a right-sided tumor (P < .001), actin-immunopositivity (P < .001), and CD34-/BCL2-immunonegativities (P = .002 and .019, respectively).
The tumor demonstrated a clonal immunoglobulin heavy chain gene rearrangement and a clonal cytogenetic abnormality including t(14;18) which was confirmed by fluorescence in situ hybridization analysis showing the IgH/BCL2 fusion gene.
Follicular lymphoma (FL), an indolent neoplasm caused by a t(14;18) chromosomal translocation that juxtaposes the BCL2 gene and immunoglobulin locus, has a variable clinical course and frequently undergoes transformation to an aggressive lymphoma.
Each set of tumors shared a common clonal origin, as demonstrated by expression of identical, unique CDR IIIH sequences, shared somatic mutations in JH, and identical bcl-2 translocation breakpoints of microdissected ALL cells.
Double-hit lymphomas (DHL) with MYC and either BCL2 or BCL6 rearrangements are rare neoplasms with an aggressive clinical presentation and grim prognosis.
Double-hit lymphomas (DHL) with chromosomal rearrangements affecting the avian myelocytomatosis viral oncogene homolog (cMYC) and either the B-cell lymphoma-2 (BCL2) or -6 (BCL6) locus are uncommon neoplasms with an aggressive clinical course and dismal prognosis.
The present study suggests that autophagy as well as the anti-apoptotic BCL-2 family members, regulated at least partly by the mTORC1 pathway downstream of STAT5/Pim-2, protects JAK2-V617F-positive leukemic cells from ruxolitinib-induced apoptosis depending on cell types and may contribute to development of new strategies against JAK2-V617F-positive neoplasms.
The mRNA expressions of miR-195, OTR, and Bax genes were significantly increased, and the mRNA expression of ERα, PI3K, NF-κB, cyclin D1 and Bcl-2 genes were decreased in the OT group in comparison with the tumor group.
Here we have shown that, in tumor samples with BCL2 translocation, those with high levels of BACH2 had significantly lower BCL2 transcript abundance compared to those with low levels of BACH2.
Considering STS patients of tumor stage 2, multivariate Cox analysis revealed that bad mRNA values > or = 10 (p=0.0039; RR=9.08), bcl-xL > or = 1.5 (p=0.067; RR=4.59), bax > or = 0.005 (p=0.1; RR=2.84) and bcl-2 < 3 (p=0.42; RR=1.7) were associated with a poor prognosis.
Testing for an IGH/BCL2 translocation should be considered in the diagnostic workup of difficult-to-characterize neoplasms with histiocytic/monocytic morphology and immunoprofile.