Rabbit Anti-Human SC35 (a.a. 131-221) Polyclonal antibody

Mutations involving epigenetic regulators (TET2 similar to 60% and ASXL1 similar to 40%) and splicing components (SRSF2 similar to 50%) are frequent in chronic myelomonocytic leukemia (CMML). On a 27-gene targeted capture panel performed on 175 CMML patients (66% males, median age 70 years), common mutations included: TET2 46%, ASXL1 47%, SRSF2 45% and SETBP1 19%. A total of 172 (98%) patients had at least one mutation, 21 (12%) had 2, 24 (14%) had 3 and 30 (17%) had 43 mutations. In a univariate analysis, the presence of ASXL1 mutations (P = 0.02) and the absence of TET2 mutations (P = 0.03), adversely impacted survival; while the number of concurrent mutations had no impact (P = 0.3). In a multivariable analysis that included hemoglobin, platelet count, absolute monocyte count and circulating immature myeloid cells (Mayo model), the presence of ASXL1 mutations (P = 0.01) and absence of TET2 mutations (P = 0.003) retained prognostic significance. Patients were stratified into four categories: ASXL1wt/TET2wt (n = 56), ASXL1mut/TET2wt (n = 31), ASXL1mut/TET2mut (n = 50) and ASXL1wt/TET2mut (n = 38). Survival data demonstrated a significant difference in favor of ASXL1wt/TET2mut (38 months; P = 0.016), compared with those with ASXL1wt/TET2wt (19 months), ASXL1mut/TET2wt (21 months) and ASXL1mut/TET2mut (16 months) (P = 0.3). We confirm the negative prognostic impact imparted by ASXL1 mutations and suggest a favorable impact from TET2 mutations in the absence of ASXL1 mutations.

Uveal Melanoma (UM) is a rare and malignant intraocular tumor with dismal prognosis. Despite the efficient control of the primary tumor by radiation or surgery, up to 50% of patients subsequently develop metastasis, mainly in the liver. Once the tumor has spread from the eye, the treatment is challenging and the median survival is only nine months. UM represents an intriguing model of oncogenesis that is characterized by a relatively homogeneous histopathological architecture and a low burden of genetic alterations, in contrast to other melanomas. UM is driven by recurrent activating mutations in G alpha q pathway, which are associated with a second mutation in BRCA1 associated protein 1 (BAP1), splicing factor 3b subunit 1 (SF3B1), or eukaryotic translation initiation factor 1A X-linked (EIF1AX), occurring in an almost mutually exclusive manner. The monosomy of chromosome 3 is also a recurrent feature that is associated with high metastatic risk. These events driving UM oncogenesis have been thoroughly investigated over the last decade. However, no efficient related therapeutic strategies are yet available and the metastatic disease remains mostly incurable. Here, we review current knowledge regarding the molecular biology and the genetics of uveal melanoma and highlight the related therapeutic applications and perspectives.