Multiple MYO18A-PDGFRB fusion transcripts in a myeloproliferative neoplasm patient with t(5;17)(q32;q11)

Sheng, Guangying; Zeng, Zhao; Pan, Jinlan; Kou, Linbing; Wang, Qinrong; Yao, Hong; Wen, Lijun; Wu, Depei; Qiu, Huiying; Chen, Suning

doi:10.1186/s13039-017-0306-8

Cited by 8 publications

(7 citation statements)

References 18 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…MYO18A (myosin XVIIIA, KIAA0216, MysPDZ) is a member of the myosin superfamily and is widely expressed in the body. In hematological malignancies, MYO18A has been found as fusions with FGFR1, PDGFRB, and MLL in other hematopoietic malignancies (Walz et al 2005; Ussowicz et al 2012; Sheng et al 2017). In all these cases, including the current one, all the predicted coiled-coil domains of normal MYO18A are retained in the fusion.…”

Section: Discussionmentioning

confidence: 99%

Two myeloid leukemia cases with rare FLT3 fusions

Zhang

Paliga

Hobbs

et al. 2018

Cold Spring Harb Mol Case Stud

View full text Add to dashboard Cite

Genetic rearrangements involving FLT3 are rare and only recently have been detected in myeloid/lymphoid neoplasms associated with eosinophilia (MLN-eos) and chronic myeloproliferative disorders. Here we report two cases with FLT3 fusions in patients demonstrating mixed features of myelodysplastic/myeloproliferative neoplasms. In the first case, FLT3 was fused with a new fusion partner MYO18A in a patient with marrow features most consistent with atypical chronic myeloid leukemia; the second case involving ETV6-FLT3 fusion was observed in a case with bone marrow features most consistent with chronic myelomonocytic leukemia. Notably, we observed that samples from both patients demonstrated FLT3 inhibitor (quizartinib and sorafenib) sensitivity in ex vivo drug screening assay.

show abstract

Section: Discussionmentioning

confidence: 99%

Two myeloid leukemia cases with rare FLT3 fusions

Zhang

Paliga

Hobbs

et al. 2018

Cold Spring Harb Mol Case Stud

View full text Add to dashboard Cite

show abstract

“…10,11,41 6.2 | Associations with cancer and neurological disease MYO18A has frequently been associated with cancer as part of gene fusions of the MYO18Aα PDZ domain with several genes including FGFR1, PDGFRB, MLL, FLT3, and ALK. [77][78][79][80][81][82] The PDZ domain of MYO18Aα interacts with the phosphoinositide lipid phosphatase PTEN suggesting a role of this domain in phosphoinositide metabolism. 83 PTEN modulates chromatin remodeling via PU.1 in hematopoietic progenitors.…”

Section: Roles In Immune Cells Of the Lymphoid Lineagementioning

confidence: 99%

Emerging concepts of myosin 18A isoform mechanobiology in organismal and immune system physiology, development, and function

DeKryger,

Chroneos

2024

The FASEB Journal

View full text Add to dashboard Cite

Alternative and combinatorial splicing of myosin 18A (MYO18A) gene transcripts results in expression of MYO18A protein isoforms and isoform variants with different membrane and subcellular localizations, and functional properties. MYO18A proteins are members of the myosin superfamily consisting of a myosin‐like motor domain, an IQ motif, and a coiled‐coil domain. MYO18A isoforms, however, lack the ability to hydrolyze ATP and do not perform ATP‐dependent motor activity. MYO18A isoforms are distinguished by different amino‐ and carboxy‐terminal extensions and domains. The domain organization and functions of MYO18Aα, MYO18Aβ, and MYO18Aγ have been studied experimentally. MYO18Aα and MYO18Aβ have a common carboxy‐terminal extension but differ by the presence or absence of an amino‐terminal KE repeat and PDZ domain, respectively. The amino‐ and carboxy‐terminal extensions of MYO18Aγ contain unique proline and serine‐rich domains. Computationally predicted MYO18Aε and MYO18Aδ isoforms contain the carboxy‐terminal serine‐rich extension but differ by the presence or absence of the amino‐terminal KE/PDZ extension. Additional isoform variants within each category arise by alternative utilization or inclusion/exclusion of small exons. MYO18Aα variants are expressed in somatic cells and mature immune cells, whereas MYO18Aβ variants occur mainly in myeloid and natural killer cells. MYO18Aγ expression is selective to cardiac and skeletal muscle. In the present review perspective, we discuss current and emerging concepts of the functional specialization of MYO18A proteins in membrane and cytoskeletal dynamics, cellular communication and signaling, endocytic and exocytic organelle movement, viral infection, and as the SP‐R210 receptor for surfactant protein A.

show abstract

“…Other gene fusion partners of PDGFRA include the breakpoint cluster region (BCR) ( Yigit et al, 2015 ), KIF5B ( Score et al, 2006 ), the CDK5 regulatory subunit associated protein 2 (CDK5RAP2) ( Walz et al, 2006 ) and the ETS variant transcription factor 6 (ETV6) ( Yoshida et al, 2015 ). As for PDGFRB, approximately 70 fusions have been identified with most fusion partners normally containing an oligomerization motif that mediates dimerization, causing continuous kinase domain activation in myeloid neoplasms ( Campregher et al, 2017 ; Sheng et al, 2017 ; Xu et al, 2020 ). Autocrine PDGFR signaling plays an essential role in cancer progression in ovarian ( Matei et al, 2006 ), breast ( Jechlinger et al, 2006 ), thyroid ( Adewuyi et al, 2018 ), and brain ( Lokker et al, 2002 ) cancers.…”

Section: Receptor Tyrosine Kinase Activationmentioning

confidence: 99%

Receptor Tyrosine Kinases and Their Signaling Pathways as Therapeutic Targets of Curcumin in Cancer

et al. 2021

View full text Add to dashboard Cite

Receptor tyrosine kinases (RTKs) are transmembrane cell-surface proteins that act as signal transducers. They regulate essential cellular processes like proliferation, apoptosis, differentiation and metabolism. RTK alteration occurs in a broad spectrum of cancers, emphasising its crucial role in cancer progression and as a suitable therapeutic target. The use of small molecule RTK inhibitors however, has been crippled by the emergence of resistance, highlighting the need for a pleiotropic anti-cancer agent that can replace or be used in combination with existing pharmacological agents to enhance treatment efficacy. Curcumin is an attractive therapeutic agent mainly due to its potent anti-cancer effects, extensive range of targets and minimal toxicity. Out of the numerous documented targets of curcumin, RTKs appear to be one of the main nodes of curcumin-mediated inhibition. Many studies have found that curcumin influences RTK activation and their downstream signaling pathways resulting in increased apoptosis, decreased proliferation and decreased migration in cancer both in vitro and in vivo. This review focused on how curcumin exhibits anti-cancer effects through inhibition of RTKs and downstream signaling pathways like the MAPK, PI3K/Akt, JAK/STAT, and NF-κB pathways. Combination studies of curcumin and RTK inhibitors were also analysed with emphasis on their common molecular targets.

show abstract

Multiple MYO18A-PDGFRB fusion transcripts in a myeloproliferative neoplasm patient with t(5;17)(q32;q11)

Cited by 8 publications

References 18 publications

Two myeloid leukemia cases with rare FLT3 fusions

Two myeloid leukemia cases with rare FLT3 fusions

Emerging concepts of myosin 18A isoform mechanobiology in organismal and immune system physiology, development, and function

Receptor Tyrosine Kinases and Their Signaling Pathways as Therapeutic Targets of Curcumin in Cancer

Contact Info

Product

Resources

About