CD135
Encyclopedia
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.
(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 progenitor
s (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.
Flt3 ligand
(Flt3L).
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).
, 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.
Sorafenib
has been reported to show significant activity against Flt3-ITD positive acute myelogenous leukemia.
Protein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...
that in humans is encoded by the FLT3 gene
Gene
A gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...
. FLT-3 is a cytokine receptor
Cytokine receptor
Cytokine receptors are receptors that bind cytokines.In recent years, the cytokine receptors have come to demand the attention of more investigators than cytokines themselves, partly because of their remarkable characteristics, and partly because a deficiency of cytokine receptors has now been...
expressed on the surface of hematopoietic progenitor cells.
Cell surface marker
Cluster of differentiationCluster of differentiation
The cluster of differentiation is a protocol used for the identification and investigation of cell surface molecules present on white blood cells, providing targets for immunophenotyping of cells...
(CD) molecules are markers on the cell surface, as recognized by specific sets of antibodies
Antibody
An antibody, also known as an immunoglobulin, is a large Y-shaped protein used by the immune system to identify and neutralize foreign objects such as bacteria and viruses. The antibody recognizes a unique part of the foreign target, termed an antigen...
, 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
Bone marrow
Bone marrow is the flexible tissue found in the interior of bones. In humans, bone marrow in large bones produces new blood cells. On average, bone marrow constitutes 4% of the total body mass of humans; in adults weighing 65 kg , bone marrow accounts for approximately 2.6 kg...
. Specifically, multipotent progenitor
Progenitor cell
A progenitor cell is a biological cell that, like a stem cell, has a tendency to differentiate into a specific type of cell, but is already more specific than a stem cell and is pushed to differentiate into its "target" cell...
s (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 cytokineCytokine
Cytokines are small cell-signaling protein molecules that are secreted by the glial cells of the nervous system and by numerous cells of the immune system and are a category of signaling molecules used extensively in intercellular communication...
Flt3 ligand
FMS-like tyrosine kinase 3 ligand
The Flt3l is a small molecule that acts as a growth factor that increases the number of immune cells by activating the hematopoietic progenitors. It also induces the mobilization of the hematopoietic progenitors and stem cells in vivo which may help the system to kill cancer cells.FLT3L is crucial...
(Flt3L).
Function
CD135 is a receptor tyrosine kinaseReceptor tyrosine kinase
Receptor tyrosine kinases s are the high-affinity cell surface receptors for many polypeptide growth factors, cytokines, and hormones. Of the 90 unique tyrosine kinase genes identified in the human genome, 58 encode receptor tyrosine kinase proteins....
type III. When this receptor binds to Flt3L it forms a dimer
Protein dimer
In biochemistry, a dimer is a macromolecular complex formed by two, usually non-covalently bound, macromolecules like proteins or nucleic acids...
with itself (homodimer
Protein dimer
In biochemistry, a dimer is a macromolecular complex formed by two, usually non-covalently bound, macromolecules like proteins or nucleic acids...
) 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
Lymphocyte
A lymphocyte is a type of white blood cell in the vertebrate immune system.Under the microscope, lymphocytes can be divided into large lymphocytes and small lymphocytes. Large granular lymphocytes include natural killer cells...
(B cell
B cell
B cells are lymphocytes that play a large role in the humoral immune response . The principal functions of B cells are to make antibodies against antigens, perform the role of antigen-presenting cells and eventually develop into memory B cells after activation by antigen interaction...
and T cell
T cell
T cells or T lymphocytes belong to a group of white blood cells known as lymphocytes, and play a central role in cell-mediated immunity. They can be distinguished from other lymphocytes, such as B cells and natural killer cells , by the presence of a T cell receptor on the cell surface. They are...
) development, but not for the development of other blood cells (myeloid
Myeloid
The term myeloid suggests an origin in the bone marrow or spinal cord, or a resemblance to the marrow or spinal cord.In hematopoiesis, the term "myeloid cell" is used to describe any leukocyte that is not a lymphocyte...
development).
Role in cancer
CD135 is a proto-oncogene, meaning that mutations of this protein can lead to cancer. Mutations of the Flt3 receptor can lead to the development of leukemiaLeukemia
Leukemia or leukaemia is a type of cancer of the blood or bone marrow characterized by an abnormal increase of immature white blood cells called "blasts". Leukemia is a broad term covering a spectrum of diseases...
, 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
Prognosis
Prognosis is a medical term to describe the likely outcome of an illness.When applied to large statistical populations, prognostic estimates can be very accurate: for example the statement "45% of patients with severe septic shock will die within 28 days" can be made with some confidence, because...
associated with adverse disease outcome.
AC220 and midostaurin
Midostaurin
Midostaurin is a multi-target protein kinase inhibitor being investigated for the treatment of acute myeloid leukemia and myelodysplastic syndrome...
are in phase II clinical trials for AML patients with FLT3 mutations.
Sorafenib
Sorafenib
Sorafenib , is a drug approved for the treatment of primary kidney cancer and advanced primary liver cancer ....
has been reported to show significant activity against Flt3-ITD positive acute myelogenous leukemia.
See also
- Cluster of differentiationCluster of differentiationThe cluster of differentiation is a protocol used for the identification and investigation of cell surface molecules present on white blood cells, providing targets for immunophenotyping of cells...
- cytokine receptorCytokine receptorCytokine receptors are receptors that bind cytokines.In recent years, the cytokine receptors have come to demand the attention of more investigators than cytokines themselves, partly because of their remarkable characteristics, and partly because a deficiency of cytokine receptors has now been...
- receptor tyrosine kinaseReceptor tyrosine kinaseReceptor tyrosine kinases s are the high-affinity cell surface receptors for many polypeptide growth factors, cytokines, and hormones. Of the 90 unique tyrosine kinase genes identified in the human genome, 58 encode receptor tyrosine kinase proteins....
- tyrosine kinaseTyrosine kinaseA tyrosine kinase is an enzyme that can transfer a phosphate group from ATP to a protein in a cell. It functions as an "on" or "off" switch in many cellular functions....
- oncogeneOncogeneAn oncogene is a gene that has the potential to cause cancer. In tumor cells, they are often mutated or expressed at high levels.An oncogene is a gene found in the chromosomes of tumor cells whose activation is associated with the initial and continuing conversion of normal cells into cancer...
- hematopoiesis