Molecular Genetic Biomarkers in Myeloid Malignancies

Abstract

Context.-Recent studies using massively parallel sequencing technologies, so-called next-generation sequencing, have uncovered numerous recurrent, single-gene variants or mutations across the spectrum of myeloid malignancies.Objectives.-To review the recent advances in the understanding of the molecular basis of myeloid neoplasms, including their significance for diagnostic and prognostic purposes and the possible implications for the development of novel therapeutic strategies.Data Sources.-Literature review.Conclusions.-The recurrent mutations found in myeloid malignancies fall into distinct functional categories.These include (1) cell signaling factors, (2) transcription factors, (3) regulators of the cell cycle, (4) regulators of DNA methylation, (5) regulators of histone modification, (6) RNA-splicing factors, and (7) components of the cohesin complex. As the clinical significance of these mutations and mutation combinations is established, testing for their presence is likely to become a routine part of the diagnostic workup. This review will attempt to establish a framework for understanding these mutations in the context of myeloproliferative neoplasms, myelodysplastic syndromes, and acute myeloid leukemia.

Trim27 confers myeloid hematopoiesis competitiveness by up-regulating myeloid master genes

“…Loss of Spi1 causes failure of myelopoiesis indicating its essential role in myeloid development. 18 Cebpg interacts with Spi1 to regulate myeloid 21,22 In addition, Trim27 up-regulated Nras, 23 Runx1, 24 and Cbfb, 25 which are involved in myeloid leukemogenesis. Consistent with the myeloid proliferation effect, Adam8 is reported to be cell surface antigen mainly expressed in monocytic lineage 26 and Dek has a positive effect on the differentiation of mature myeloid cells.…”

“…Moreover, expression level of the following myeloid related genes was significantly elevated in the Trim27‐overexpressing MP population. Socs2, Socs3 , and Cish are negative regulators of JAK/STAT signaling in myeloproliferative neoplasm and their up‐regulation indicates hyper‐activated JAK/STAT signaling . In addition, Trim27 up‐regulated Nras , Runx1 , and Cbfb , which are involved in myeloid leukemogenesis.…”

Latest Implications of Next-Gen Sequencing in Diagnosis of Acute and Chronic Myeloid Leukemia

“…The most common Next-Gen Sequencing platform currently on the market are offered by Illumina (San Diego, CA, USA), being represented by iSeq100, miniSeq, miSeq, nextSeq System, HiSeq2500, HiSeqX Ten, and NovaSeq, and Thermo Fisher Scientific (Waltham, MA, USA) offers the Ion Proton System, Ion PGM System, Ion S5 System, Ion S5 XL System, Ion GeneStudio S5 System, and the HID GeneStudio A comparison between these panels is described succinctly by Matynia et al [12] in Table 1.…”

Molecular Genetic Abnormalities in the Pathogenesis of Hematologic Malignancies and Corresponding Changes in Cell Signaling Systems

“…Нарушается эпигенетическая регуляция экспрессии генов [34] ОМЛ с изменениями, связанными с миелодисплазией Т-и В-клеточные опухоли, в свою очередь, подразде-ляются на развивающиеся из клеток-предшественниц или лимфобластные (острый лимфобластный лейкоз) и из зрелых периферических В-и Т-клеток [7,9]. Решающее событие в развитии Т-лимфоцитов -формирование антигенраспознающего Т-клеточного рецептора (TCR).…”