Arguably the MYC activity gain is the most constantly observed phenomenon (>70% of cases) in transformed FL/MALT/CLL (Richter's transformation) and co-occurs with specific aberrations such as the loss of p53, CDKN2A/B, or gain of BCL2/BCL6.
Spontaneously regressed CLL displayed a transcriptome profile characterized by downregulation of metabolic processes as well as MYC and its downstream targets compared to non-regressing CLL.
Accordingly, siRNA-mediated downregulation of either <i>EZH2, MYC</i> or <i>IGF1R</i> and treatment with EZH2 and MYC pharmacological inhibitors in the HG3 CLL cell line induced a significant reduction in PI3K pathway activation.
In conclusion, NOTCH1 mutations in CLL are associated with the overexpression of MYC and MYC-related genes involved in protein biosynthesis including NPM1, which are allegedly responsible for cell growth and/or proliferation advantages of NOTCH1-mut CLL.
Additionally, following downregulation of Notch 2 protein expression, the protein expression levels of phospho‑mitogen‑activated protein kinase 1 (p‑ERK), v‑myc avian myelocytomatosis viral oncogene homolog and B‑cell CLL/lymphoma 2 (Bcl2) were also downregulated, whereas, Bcl2‑associated X protein expression was upregulated.
In this issue of Blood, Yeomans et al identify MYC as an important target for translational regulation in chronic lymphocytic leukemia (CLL) cells after B-cell receptor (BCR) stimulation and show that current therapies suppress this induction.
Additionally, MYC rearranged CLL presented as outstanding group by often showing a non-complex karyotype (85%), absence of ID3 mutations, a high frequency of SF3B1 mutations, and a frequent involvement of non-immunoglobulin loci as MYC-partner genes (61%).
These include previously unrecognized putative cancer drivers (RPS15, IKZF3), and collectively identify RNA processing and export, MYC activity, and MAPK signalling as central pathways involved in CLL.
Genome-wide association studies (GWAS) have identified that a ∼1 M region centromeric to the MYC oncogene on chromosome 8q24.21 harbors at least five independent loci associated with prostate cancer risk and additional loci associated with cancers of breast, colon, bladder, and chronic lymphocytic leukemia (CLL).
We report the characteristics of 21 patients with CLL and nine patients with prolymphocytic leukemia (PLL), diagnosed in multiple centers (n = 13), which showed an MYC translocation demonstrated by fluorescence in situ hybridization.The prevalence was estimated to be <1%.
This study reveals an important relationship between BAFF and c-MYC in CLL which may affect disease development and progression, and suggests that inhibitors of the canonical NF-κB pathway may be effective in treatment of patients with this disease.
Based upon these results, we propose for the first time that miR-196b has the inherent capacity to down-regulate the overamplified c-myc gene recognized as a common pathognomonic feature leading to cancer in general and B-cell ALL in particular.
A deregulation of MYC pathway might represent one of the main transformation events in the pathogenesis of a subset of RS clonally related to the previous CLL.
U-2973, a novel B-cell line established from a patient with a mature B-cell leukemia displaying concurrent t(14;18) and MYC translocation to a non-IG gene partner.
The rarity of t(8;14) in CLL together with a cryptic deletion that probably includes the MYC gene in our CLL patient persuaded us to explore the clinicopathological role of MYC translocations by comparing disease progression in our patient and in other reported CLL cases.
Translocations involving an overexpressed c-myc gene are also found in AIDS-associated lymphoma or in T cell leukaemias, or they develop during tumour progression of a low grade B cell malignancy into a high grade B cell tumour in an additional cytogenetic change.
A chromosome 12 coding region is juxtaposed to the MYC protooncogene locus in a t(8;12)(q24;q22) translocation in a case of B-cell chronic lymphocytic leukemia.
Because the numbers of peripheral blood lymphoma cells were independent of tumor mass and of c-myc gene transcripts expressed, peripheral blood lymphocytosis might more likely reflect homing processes than proliferative activity in CLL.