Chronic lymphocytic leukemia (CLL) is the most common leukemia in adults in the Western hemisphere. Its clinical course is heterogeneous and difficult to predict; overall survival (OS) after diagnosis varies considerably (from <2 years to decades), making such predictions of utmost importance. Some patients diagnosed with Rai stage 0 (lymphocytosis of e5,000 B lymphocytes/?L) or 1 (lymphocytosis with lymphadenopathy) never need treatment; others progress rapidly. Generally accepted guidelines recommend starting treatment only after disease progression (characterized by development of anemia, or lymphadenopathy, among other signs). We and others have shown that an intricate interplay between abnormalities in protein-coding genes (PCGs) and non-coding RNAs (ncRNAs) is causally involved in CLL initiation, and progression. We hypothesize that the risk of progression is related to intrinsic biologic characteristics (e.g. expression of PG or ncRNA from malignant B cells as well as from viral origin) of the CLL clone that exists early in the disease course. Thus, it should be possible to distinguish patients who are at risk of progression from patients with indolent CLL (defined as stable Rai stage 0/I disease not requiring therapy for e5 years after diagnosis). Patients diagnosed with any stage of CLL, before or after treatment, may undergo a Richter's transformation (RT); they develop an aggressive diffuse large B-cell lymphoma that is typically therapy resistant and associated with short OS. About 80-90% of RT is clonally related to the CLL clone. We hypothesize that the risk to develop RT is associated with intrinsic biologic characteristics of the CLL clone before transformation. Thus, it should be possible to identify those patients who are at risk of RT early in the disease course. None of the present used clinical markers can do this with high accuracy. This proposal's goal is to focus on this challenging subset of clinically early stage cases to identify expression signatures of coding and non-coding RNA transcripts, elucidate their roles in disease progression, and their clinical significance as biomarkers of early diagnosis. Our long-term goal is to find interact or pairs of microRNAs and target PCGs with key roles in the onset of disease, understand their mechanisms of action, and use the acquired knowledge to develop new diagnostic and prognostic tools.
Chronic lymphocytic leukemia (CLL) is the most common leukemia and is characterized by a highly variable clinical outcome difficult to predict. We and others have shown that an intricate interplay between abnormalities in protein-coding genes (PCGs) and non-coding RNAs (ncRNAs) is causally involved in CLL initiation and progression. We hypothesize that disease progression and transformation are related to intrinsic biologic characteristics (e.g., expression of PCGs and ncRNAs of cellular and viral origin) of the CLL clone that exist in the earliest stages of disease course.
|Wang, Min; Abrams, Zachary B; Kornblau, Steven M et al. (2018) Thresher: determining the number of clusters while removing outliers. BMC Bioinformatics 19:9|
|Abruzzo, Lynne V; Herling, Carmen D; Calin, George A et al. (2018) Trisomy 12 chronic lymphocytic leukemia expresses a unique set of activated and targetable pathways. Haematologica :|
|Shah, Maitri Y; Ferracin, Manuela; Pileczki, Valentina et al. (2018) Cancer-associated rs6983267 SNP and its accompanying long noncoding RNA CCAT2 induce myeloid malignancies via unique SNP-specific RNA mutations. Genome Res 28:432-447|
|Abrams, Zachary B; Zucker, Mark; Wang, Min et al. (2018) Thirty biologically interpretable clusters of transcription factors distinguish cancer type. BMC Genomics 19:738|
|Velazquez-Torres, Guermarie; Shoshan, Einav; Ivan, Cristina et al. (2018) A-to-I miR-378a-3p editing can prevent melanoma progression via regulation of PARVA expression. Nat Commun 9:461|
|Anfossi, Simone; Fu, Xiao; Nagvekar, Rahul et al. (2018) MicroRNAs, Regulatory Messengers Inside and Outside Cancer Cells. Adv Exp Med Biol 1056:87-108|
|Wang, Min; Kornblau, Steven M; Coombes, Kevin R (2018) Decomposing the Apoptosis Pathway Into Biologically Interpretable Principal Components. Cancer Inform 17:1176935118771082|
|Dragomir, Mihnea; Chen, Baoqing; Calin, George A (2018) Exosomal lncRNAs as new players in cell-to-cell communication. Transl Cancer Res 7:S243-S252|
|Monroig-Bosque, Paloma Del C; Shah, Maitri Y; Fu, Xiao et al. (2018) OncomiR-10b hijacks the small molecule inhibitor linifanib in human cancers. Sci Rep 8:13106|
|Silva, Andreia M; Almeida, Maria I; Teixeira, José H et al. (2018) Profiling the circulating miRnome reveals a temporal regulation of the bone injury response. Theranostics 8:3902-3917|
Showing the most recent 10 out of 79 publications