scholarly journals Genetic Biomarkers in Chronic Myeloid Leukemia: What Have We Learned So Far?

2021 ◽  
Vol 22 (22) ◽  
pp. 12516
Author(s):  
Bilal Abdulmawjood ◽  
Beatriz Costa ◽  
Catarina Roma-Rodrigues ◽  
Pedro V. Baptista ◽  
Alexandra R. Fernandes
Keyword(s):  
Growth Factor ◽  
Chronic Myeloid Leukemia ◽  
Transforming Growth Factor Beta ◽  
Myeloid Leukemia ◽  
Transforming Growth Factor ◽  
Fusion Gene ◽  
Philadelphia Chromosome ◽  
Growth Factor Receptor ◽  
Disease States ◽  
Growth Factor Beta

Chronic Myeloid Leukemia (CML) is a rare malignant proliferative disease of the hematopoietic system, whose molecular hallmark is the Philadelphia chromosome (Ph). The Ph chromosome originates an aberrant fusion gene with abnormal kinase activity, leading to the buildup of reactive oxygen species and genetic instability of relevance in disease progression. Several genetic abnormalities have been correlated with CML in the blast phase, including chromosomal aberrations and common altered genes. Some of these genes are involved in the regulation of cell apoptosis and proliferation, such as the epidermal growth factor receptor (EGFR), tumor protein p53 (TP53), or Schmidt-Ruppin A-2 proto-oncogene (SRC); cell adhesion, e.g., catenin beta 1(CTNNB1); or genes associated to TGF-β, such as SKI like proto-oncogene (SKIL), transforming growth factor beta 1 (TGFB1) or transforming growth factor beta 2 (TGFB2); and TNF-α pathways, such as Tumor necrosis factor (TNFA) or Nuclear factor kappa B subunit 1 (NFKB1). The involvement of miRNAs in CML is also gaining momentum, where dysregulation of some critical miRNAs, such as miRNA-451 and miRNA-21, which have been associated to the molecular modulation of pathogenesis, progression of disease states, and response to therapeutics. In this review, the most relevant genomic alterations found in CML will be addressed.

A Study of Burns for Wound Ageing reveals Changes in Unburnt Skin with Implications for Future Research

2005 ◽  
Vol 45 (3) ◽  
pp. 205-210 ◽  
Author(s):  
Neil E I Langlois ◽  
Sarah Tarran ◽  
Peter Dziewulski
Keyword(s):  
Epidermal Growth Factor Receptor ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Growth Factor Receptor ◽  
Burn Wounds ◽  
Epidermal Growth ◽  
Growth Factor Beta ◽  
Mib 1

Thirty-three punch biopsy sets of burn wound edge and adjacent unburnt skin from burn wounds aged six hours to 23 days were obtained from 18 patients. Immunohistochemical staining was performed for transforming growth factor beta receptor, epidermal growth factor receptor and MIB-1 (which stains the cell cycle associated antigen ki-67) in addition to integrins alpha V, 5 and 3 to assess for temporal patterns that might assist in the ageing of burn wounds. There was an early (12 hr-4 day) rise in integrin alpha V expression, an increasing expression of transforming growth factor beta receptor from 12 hours onwards, and increased expression of MIB-1 commencing at 2 days. In biopsy samples from the edge of the burn there was a trend for an early (6 hr-4 day) rise in epidermal growth factor receptor expression. There were no discernable changes in integrin alpha 5 or 3. The striking feature was that biopsy samples from the adjacent, unburnt skin showed similar temporal staining patterns. A further study would be required to determine if the effect was generalised or local, but the observation of changes in unburnt tissue implies that careful consideration must be given to selecting control tissue.

scholarly journals Basolateral delivery of the type I transforming growth factor beta receptor is mediated by a dominant-acting cytoplasmic motif

2017 ◽  
Vol 28 (20) ◽  
pp. 2701-2711 ◽  
Author(s):  
Xueqian Yin ◽  
Jeong-Han Kang ◽  
Mahefatiana Andrianifahanana ◽  
Youli Wang ◽  
Mi-Yeon Jung ◽  
...  
Keyword(s):  
Amino Acids ◽  
Growth Factor ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Point Mutations ◽  
Growth Factor Receptor ◽  
Receptor Expression ◽  
Receptor Internalization ◽  
Type I ◽  
Growth Factor Beta

Delivery of biomolecules to the correct subcellular locales is critical for proper physiological function. To that end, we have previously determined that type I and II transforming growth factor beta (TGF-β) receptors (TβRI and TβRII, respectively) localize to the basolateral domain in polarized epithelia. While TβRII targeting was shown to be regulated by sequences between amino acids 529 and 538, the analogous region(s) within TβRI is unknown. To address that question, sequential cytoplasmic TβRI truncations and point mutations identified a targeting motif between residues 158 and 163 (VxxEED) required for basolateral TβRI expression. Further studies documented that receptor internalization, down-regulation, direct recycling, or Smad signaling were unaffected by motif mutations that caused TβRI mislocalization. However, inclusion of amino acids 148–217 containing the targeting motif was able to direct basolateral expression of the apically sorted nerve growth factor receptor (NGFR, p75; extracellular and transmembrane regions) in a dominant manner. Finally, coexpression of apically targeted type I and type II TGF-β receptors mediated Smad3 signaling from the apical membrane of polarized epithelial cells. These findings demonstrate that the absence of apical TGF-β signaling in normal epithelia is primarily a reflection of domain-specific receptor expression and not an inability to couple with the signaling machinery.

scholarly journals Hematopoietic cytokines inhibit apoptosis induced by transforming growth factor beta 1 and cancer chemotherapy compounds in myeloid leukemic cells

Blood ◽  
1992 ◽  
Vol 80 (7) ◽  
pp. 1750-1757 ◽  
Author(s):  
J Lotem ◽  
L Sachs
Keyword(s):  
Growth Factor ◽  
Transforming Growth Factor Beta ◽  
Myeloid Leukemia ◽  
Transforming Growth Factor ◽  
Leukemic Cells ◽  
Tgf Beta ◽  
Gm Csf ◽  
Cytotoxic Compounds ◽  
Growth Factor Beta ◽  
Induction Of Apoptosis

Transforming growth factor-beta 1 (TGF-beta 1) induces cell death in myeloid leukemia by apoptosis. In the M1 myeloid leukemia, this induction of apoptosis was inhibited by granulocyte colony-stimulating factor (G-CSF) or interleukin-6 (IL-6) and to a lesser extent by IL-1 alpha. IL-3 and stem cell factor/mast cell growth factor (SCF) showed only a marginal effect, and granulocyte-macrophage and macrophage CSFs (GM-CSF and M-CSF, respectively) were inactive. The induction of apoptosis by TGF-beta 1 in a different myeloid leukemia (7-M12) was inhibited by GM-CSF and IL-3 but not by the other cytokines. In the absence of TGF-beta 1, both M1 and 7-M12 leukemic cells were independent of hematopoietic cytokines for cell viability and growth. The cytotoxic compounds vincristine, vinblastine, adriamycin, cytosine arabinoside, cycloheximide, and sodium azide, some of which are used in cancer chemotherapy, induced cell death by apoptosis in both leukemias. As with TGF-beta 1, apoptosis induced by these cytotoxic compounds was inhibited by GM-CSF (7-M12 leukemia) and by G-CSF or IL-6 (M1 leukemia). Cyclosporine A decreased cell multiplication in M1 cells without inducing apoptosis, and G-CSF and IL-6 inhibited the cytostatic effect of cyclosporine A. It is suggested that the clinical use of cytokines to correct therapy-associated myelosuppression should be carefully timed to avoid protection of malignant cells from the cytotoxic action of the therapeutic compounds.

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