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Oncogenes and tumor suppressor genes
Published in A. R. Genazzani, Hormone Replacement Therapy and Cancer, 2020
S. Giordano, S. Corso, P. Conrotto
Several oncogenes encode non-receptor protein tyrosine kinases. One of these is generated by a chromosomal translocation, resulting in fusion of a portion of the bcr gene with part of the abl gene, that encodes a soluble tyrosine kinase. This translocation is a marker for chronic myelogenous leukemia and leads to the production of a constitu tively active kinase. This fusion protein, as shown also by experiments in transgenic mice expressing the bcr-abl gene, is responsible for the initial chronic phase of the leukemia.
Monocyte and lymphocyte membrane markers: Ontogeny and clinical significance
Published in Gabriel Virella, Medical Immunology, 2019
Scott Sugden, Damien Montamat-Sicotte, Karen K. Yam, Joseph Murphy, Bader Yassine Diab, Virginia Litwin
The immature B cells are CD19+, sIgMhigh, sIgDlow, CD21−, CD23−. They most likely undergo clonal deletion or anergy as evident by their lack of expression of survival factor, Bcl-2, and high expression of the pro-apoptotic molecule, CD95 (FAS). The surviving cells display a phenotype close to that of a mature B cell, CD19+, sIgMhigh, sIgDlow, CD21high, and CD23high. BCR signaling of these cells results in extensive proliferation.
Practical Approach to Molecular Biology in Hematopathology
Published in Harold R. Schumacher, William A. Rock, Sanford A. Stass, Handbook of Hematologic Pathology, 2019
Anwar Mikhael, Harold R. Schumacher
As a consequence of the translocation, sequences of the ABL proto-oncogene are moved from chromosome 9 to chromosome 22, where they are located in the 3’ region of the BCR gene. The breakpoints on chromosome 9 are widely distributed and range from about 15 to over 40 kb upstream of the most proximal region (first exon) of the ABL gene. However, the breakpoint on chromosome 22 occurs over a much shorter region of approximately 5–10 kb. This region is referred as the major breakpoint cluster region (M-bcr) (11).
Anticancer Activity and Molecular Mechanism of Momordica cochinchinensis Seed Extract in Chronic Myeloid Leukemia Cells
Published in Nutrition and Cancer, 2022
Zhengdong Ai, Chong Ma, Ruiming Wan, Jingyi Yin, Guiming Li, Yan Li, Li Chen
The formation of Bcr-Abl is the pathogenesis of chronic myeloid leukemia. Targeting Bcr-Abl is the key to treating CML patients. Therefore, a plasmid for determining the reporter activity of the Bcr-Abl promoter was established by incorporating the Bcr-Abl promoter region (approximately 2000 base pairs) into firefly luciferase expression plasmid (pGL3-Basic, Promega), by which the inhibitory activity of MCSE against Bcr-Abl transcription was examined. The results demonstrated that MCSE significantly inhibited the Bcr-Abl promoter activity (Figure 2A) in HEK-293T cells. Meanwhile, the expression levels of Bcr-Abl in two CML cell lines KBM5 and KBM5-T315I were investigated after CML cells were treated with different concentrations (0, 20, 40 and 60 μg/ml) of MCSE by RT-qPCR. The results were consistent with expectations that MCSE effectively inhibited the transcription of the Bcr-Abl gene in a concentration-dependent manner (Figure 2B). The inhibitory effect of MCSE on Bcr-Abl transcription in CML cells is stronger than that of MCSE on Bcr-Abl promoter activity in HEK-293T cells, indicating that MCSE may affect the level of Bcr-Abl mRNA from other aspects such as stability in CML cells.
Chronic myelomonocytic leukemia - a review
Published in Expert Review of Hematology, 2021
Thomas P. Thomopoulos, Anthi Bouhla, Sotirios G. Papageorgiou, Vasiliki Pappa
Once reactive monocytosis is excluded, a thorough assessment for an underlying clonal hematopoietic disorder must be made. Cases of chronic myeloid leukemia (CML) accompanied by marked monocytosis are easily excluded by the absence of BCR-ABL1 fusion gene. In cases of prominent eosinophilia, a myeloid/lymphoid neoplasm with eosinophilia should be excluded, by the absence of PDGFRA, PDGFRB, or FGFR1 rearrangements and PCM1-JAK2 gene fusion, as well [1]. Notably, presence of the ETV6-PDGFRB fusion gene is associated with a CMML-like phenotype with prominent eosinophilia [5]. As core-binding factor acute myeloid leukemia (AML) may be also characterized by monocytosis and eosinophilia, disease-defining rearrangements, including inv(16)(p13.1q22) must also be excluded. Rare cases of BCR/ABL1 negative myeloproliferative neoplasms (MPN) with monocytosis at presentation should also be excluded; presence of JAK2 mutation, or other known driver mutation, thrombocytosis, or elevated levels of hemoglobin, and absence of dysplastic features are clues favoring the diagnosis of a classical MPN. It should be noted that presence of dysplastic features in bone marrow is required for establishment of CMML diagnosis. In cases with minimal or absent myelodysplasia, diagnosis is based on presence of clonal cytogenetic or molecular abnormalities [1]. Based on the peripheral WBC count, CMML cases can be subdivided into myelodysplastic CMML (MD-CMML) and myeloproliferative CMML (MP-CMML) (WBC<13 × 109/L and WBC ≥ 13 × 109/L, respectively) [6].
Current strategies for detecting functional convergence across B-cell receptor repertoires
Published in mAbs, 2021
Matthew I. J. Raybould, Anthony R. Rees, Charlotte M. Deane
In this review, we start by recapping the immunogenomic mechanisms that contribute to the theoretical BCR repertoire sequence diversity of different B-cell compartments and outline the case for why, even though individuals’ B-cell repertoires sample only a tiny fraction of the theoretical BCR diversity at any one time,8 we might still expect to observe the significant functional commonalities that are seen between different individuals. We then cover key considerations when designing a robust repertoire analysis study, and how they influence the likelihood/significance of observing functional commonality. These include donor recruitment and stratification, B-cell extraction regimen, B-cell sorting, B-cell sequencing, and finally choosing appropriate computational tools with which to functionally cluster the BCR-seq data. Finally, we discuss potential methods to further improve BCR functional clustering protocols.