Abstract
B-cell and T-cell lymphomas and leukemias often have distinct genetic mutations that are diagnostically defining or prognostically significant. A subset of these mutations consists of specific point mutations, which can be evaluated using genetic sequencing approaches or point mutation specific antibodies. Here, we describe genes harboring point mutations relevant to B-cell and T-cell malignancies and discuss the current availability of these targeted point mutation specific antibodies. We also evaluate the possibility of generating novel antibodies against known point mutations by computationally assessing for chemical and structural features as well as epitope antigenicity of these targets. Our results not only summarize several genetic mutations and identify existing point mutation specific antibodies relevant to hematologic malignancies, but also reveal potential underdeveloped targets which merit further study.
Highlights
In 2016, the World Health Organization (WHO) revised the fourth edition of the WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues based on new molecular and morphological findings [1]
Most of the mutations found in this gene occur in exon 15 which results in a valine to glutamic acid substitution at codon 600 (i.e., V600E) and is thought to mimic phosphorylation of the activation site [20]
In B-cell neoplasms, BRAF V600E mutations are highly sensitive for hairy cell leukemia (HCL), seen in essentially 100% of cases
Summary
In 2016, the World Health Organization (WHO) revised the fourth edition of the WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues based on new molecular and morphological findings [1]. The revised criteria for numerous hematopoietic malignancies indicate that genetic mutations play a significant role in the diagnosis of these entities. Many of these mutations are well-defined recurrent point mutations in specific genes. The ability to use antibodies in hematologic malignancies would provide benefit both in research and clinical settings. MaterTiahles apnodteMntieatlhfoodrspoint mutation specific antibody production of the selected genes 2.1.wTarsgaetssSeeslescetdionby using peptide sequences from the associated proteins that contained thFeormouutratsetdudaym, iwnoe asecliedcst,edwhgiecnheswweriethidkennotwifinedpouisnitngmuNtCatBioI’nssGtheantBhanavkeabnedenUdneiP-rot. Changes in relative solvent accessibility (RSA) ranging from 0 (completely buried) to 9 (fully exposed) along with physical and chemical properties (hydrophobicity, polarity, and charge) identified interaction interfaces along the peptide These interaction interfaces are essential for predicting antibody-native protein reactivity.
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