CD135

Fms-related tyrosine kinase 3
Identifiers
Symbols FLT3; CD135; FLK2; STK1
External IDs OMIM136351 MGI95559 HomoloGene3040 GeneCards: FLT3 Gene
EC number 2.7.10.1
RNA expression pattern
More reference expression data
Orthologs
Species Human Mouse
Entrez 2322 14255
Ensembl ENSG00000122025 ENSMUSG00000042817
UniProt P36888 Q2VPD1
RefSeq (mRNA) NM_004119.2 NM_010229.2
RefSeq (protein) NP_004110.2 NP_034359.2
Location (UCSC) Chr 13:
28.58 – 28.67 Mb
Chr 5:
148.14 – 148.21 Mb
PubMed search [1] [2]

Cluster of differentiation antigen 135 (CD135) also known as Fms-like tyrosine kinase 3 (FLT-3) or receptor-type tyrosine-protein kinase FLT3 is a protein that in humans is encoded by the FLT3 gene. FLT-3 is a cytokine receptor expressed on the surface of hematopoietic progenitor cells.

Contents

Synonyms

fms-like tyrosine kinase receptor-3 (Flt3), fetal liver kinase-2 (Flk2)

Cell surface marker

Cluster of differentiation (CD) molecules are markers on the cell surface, as recognized by specific sets of antibodies, used to identify the cell type, stage of differentiation and activity of a cell. CD135 is an important cell surface marker used to identify certain types of hematopoietic (blood) progenitors in the bone marrow. Specifically, multipotent progenitors (MPP) and common lymphoid progenitors (CLP) express high surface levels of CD135. This marker is therefore used to differentiate hematopoietic stem cells (HSC), which are CD135 negative, from MPPs, which are CD135 positive.

Ligand

CD135 is the receptor for the cytokine Flt3 ligand (Flt3L).

Function

CD135 is a receptor tyrosine kinase type III. When this receptor binds to Flt3L it forms a dimer with itself (homodimer) that activates its intrinsic tyrosine kinase activity, which in turn phosphorylates and activates signal transduction molecules that propagate the signal in the cell. Signaling through CD135 plays a role in cell survival, proliferation, and differentiation. CD135 is important for lymphocyte (B cell and T cell) development, but not for the development of other blood cells (myeloid development).

Role in cancer

CD135 is a proto-oncogene, meaning that mutations of this protein can lead to cancer[1]. Mutations of the Flt3 receptor can lead to the development of leukemia, a cancer of bone marrow hematopoietic progenitors. Internal tandem duplications of Flt3 (Flt3-ITD) are the most common mutations associated with acute myelogenous leukemia (AML) and are a prognostic indicator associated with adverse disease outcome.

AC220 and midostaurin are in phase II clinical trials for AML patients with FLT3 mutations.[2][3]

Sorafenib has been reported to show significant activity against Flt3-ITD positive acute myelogenous leukemia.[4][5]

See also

References

  1. ^ FLT3 (FMS-like tyrosine kinase 3)
  2. ^ http://clinicaltrials.gov/ct2/show/NCT00989261 "Efficacy Study for AC220 to Treat Acute Myeloid Leukemia (AML) (ACE)"
  3. ^ http://www.genengnews.com/news/bnitem.aspx?name=71385927 "Astellas Pays $40M Up Front to Develop Ambit’s FLT3 Kinase Inhibitors"
  4. ^ Metzelder S, Wang Y, Wollmer E, Wanzel M, Teichler S, Chaturvedi A, Eilers M, Enghofer E, Neubauer A, Burchert A (June 2009). "Compassionate use of sorafenib in FLT3-ITD-positive acute myeloid leukemia: sustained regression before and after allogeneic stem cell transplantation". Blood 113 (26): 6567–71. doi:10.1182/blood-2009-03-208298. PMID 19389879. 
  5. ^ Zhang W, Konopleva M, Shi YX, McQueen T, Harris D, Ling X, Estrov Z, Quintás-Cardama A, Small D, Cortes J, Andreeff M (February 2008). "Mutant FLT3: a direct target of sorafenib in acute myelogenous leukemia". J. Natl. Cancer Inst. 100 (3): 184–98. doi:10.1093/jnci/djm328. PMID 18230792. 

Further reading

External links