The Ubiquitin-Conjugating Enzyme E2 O (UBE2O) and Its Therapeutic Potential in Human Leukemias and Solid Tumors.

Protein degradation is a biological phenomenon essential for cellular homeostasis and survival. Selective protein degradation is performed by the ubiquitination system which selectively targets proteins that need to be eliminated and leads them to proteasome degradation. In this narrative review, we focus on the ubiquitin-conjugating enzyme E2 O (UBE2O) and highlight the role of UBE2O in many biological and physiological processes.

A Leukemic Target with a Thousand Faces: The Mitochondria.

In the era of personalized medicine greatly improved by molecular diagnosis and tailor-made therapies, the survival rate of acute myeloid leukemia (AML) at 5 years remains unfortunately low. Indeed, the high heterogeneity of AML clones with distinct metabolic and molecular profiles allows them to survive the chemotherapy-induced changes, thus leading to resistance, clonal evolution, and relapse. Moreover, leukemic stem cells (LSCs), the quiescent reservoir of residual disease, can persist for a long time and activate the recurrence of disease, supported by significant metabolic differences compared to AML blasts.

IκBα targeting promotes oxidative stress-dependent cell death.

Background: Oxidative stress is a hallmark of many cancers. The increment in reactive oxygen species (ROS), resulting from an increased mitochondrial respiration, is the major cause of oxidative stress. Cell fate is known to be intricately linked to the amount of ROS produced.

Non-Coding RNAs: The "Dark Side Matter" of the CLL Universe.

For many years in the field of onco-hematology much attention has been given to mutations in protein-coding genes or to genetic alterations, including large chromosomal losses or rearrangements. Despite this, biological and clinical needs in this sector remain unmet. Therefore, it is not surprising that recent studies have shifted from coded to non-coded matter.

P53 vs NF-κB: the role of nuclear factor-kappa B in the regulation of p53 activity and vice versa.

The onco-suppressor p53 is a transcription factor that regulates a wide spectrum of genes involved in various cellular functions including apoptosis, cell cycle arrest, senescence, autophagy, DNA repair and angiogenesis. p53 and NF-κB generally have opposing effects in cancer cells. While p53 activity is associated with apoptosis induction, the stimulation of NF-κB has been demonstrated to promote resistance to programmed cell death.

Tumor Suppressors in Chronic Lymphocytic Leukemia: From Lost Partners to Active Targets.

Tumor suppressors play an important role in cancer pathogenesis and in the modulation of resistance to treatments. Loss of function of the proteins encoded by tumor suppressors, through genomic inactivation of the gene, disable all the controls that balance growth, survival, and apoptosis, promoting cancer transformation. Parallel to genetic impairments, tumor suppressor products may also be functionally inactivated in the absence of mutations/deletions upon post-transcriptional and post-translational modifications.

Inhibition of bromodomain and extra-terminal proteins increases sensitivity to venetoclax in chronic lymphocytic leukaemia.

The development of drugs able to target BTK, PI3k-delta and BCL2 has dramatically improved chronic lymphocytic leukaemia (CLL) therapies. However, drug resistance to these therapies has already been reported due to non-recurrent changes in oncogenic pathways and genes expression signatures. In this study, we investigated the cooperative role of the BCL2 inhibitor venetoclax and the BRD4 inhibitor JQ1.

Strategies For Targeting Chronic Myeloid Leukaemia Stem Cells.

Chronic Myeloid Leukaemia is a myeloproliferative disorder driven by the t(9;22) chromosomal translocation coding for the chimeric protein BCR-ABL. CML treatment represents the paradigm of molecular therapy of cancer. Since the development of the tyrosine kinase inhibitor of the BCR-ABL kinase, the clinical approach to CML has dramatically changed, with a stunning improvement in the quality of life and response rates of patients.