Chemokine (C-C motif) ligand 9 (CCL9) is a small

cytokine Cytokines are a broad and loose category of small proteins (~5–25 kDa) important in cell signaling. Cytokines are peptides and cannot cross the lipid bilayer of cells to enter the cytoplasm. Cytokines have been shown to be involved in a ...

belonging to the CC

chemokine Chemokines (), or chemotactic cytokines, are a family of small cytokines or Cell signaling, signaling proteins secreted by Cell (biology), cells that induce directional movement of leukocytes, as well as other cell types, including endothelial a ...

family. It is also called ''macrophage inflammatory protein-1 gamma'' (MIP-1γ), ''macrophage inflammatory protein-related protein-2'' (MRP-2) and CCF18, that has been described in rodents. CCL9 has also been previously designated CCL10, although this name is no longer in use. It is secreted by follicle-associated epithelium (FAE) such as that found around Peyer's patches, and attracts

dendritic cell Dendritic cells (DCs) are antigen-presenting cells (also known as ''accessory cells'') of the mammalian immune system. Their main function is to process antigen material and present it on the cell surface to the T cells of the immune system. ...

s that possess the cell surface molecule CD11b and the

chemokine receptor Chemokine receptors are cytokine receptors found on the surface of certain cells that interact with a type of cytokine called a chemokine. There have been 20 distinct chemokine receptors discovered in humans. Each has a rhodopsin-like 7- tr ...

CCR1. CCL9 can activate

osteoclast An osteoclast () is a type of bone cell that breaks down bone tissue. This function is critical in the maintenance, repair, and remodeling of bones of the vertebral skeleton. The osteoclast disassembles and digests the composite of hydrated ...

s through its receptor CCR1 (the most abundant chemokine receptor found on osteoclasts) suggesting an important role for CCL9 in

bone resorption Bone resorption is resorption of bone tissue, that is, the process by which osteoclasts break down the tissue in bones and release the minerals, resulting in a transfer of calcium from bone tissue to the blood. The osteoclasts are multi-n ...

. CCL9 is constitutively expressed in macrophages and myeloid cells. The

gene In biology, the word gene (from , ; "... Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a b ...

for CCL9 is located on

chromosome A chromosome is a long DNA molecule with part or all of the genetic material of an organism. In most chromosomes the very long thin DNA fibers are coated with packaging proteins; in eukaryotic cells the most important of these proteins ar ...

11 in mice. CCL9 is a chemokine involved in the process of signaling an antileukemic response and is a potential form of immunotherapy for

chronic myelogenous leukemia Chronic myelogenous leukemia (CML), also known as chronic myeloid leukemia, is a cancer of the white blood cells. It is a form of leukemia characterized by the increased and unregulated growth of myeloid cells in the bone marrow and the accumula ...

(CML). CML is a type of cancer in which the bone marrow produces too many red blood cells. This is caused by

chromosomal translocation In genetics, chromosome translocation is a phenomenon that results in unusual rearrangement of chromosomes. This includes balanced and unbalanced translocation, with two main types: reciprocal-, and Robertsonian translocation. Reciprocal translo ...

, a mutation in which the abnormal gene BCR-ABL, is turned into a CML cell. CML starts off as a myeloproliferative for example in

sickle cell anemia Sickle cell disease (SCD) is a group of blood disorders typically inherited from a person's parents. The most common type is known as sickle cell anaemia. It results in an abnormality in the oxygen-carrying protein haemoglobin found in red b ...

or extreme granulocytosis but if left untreated, it could transform into an acute form of leukemia. In order to treat CML, alpha and beta interferons (INFs) are used to regulate the process of binding the protein ICSBP to the gene BCR-ABL. CCL9 was proved to be a gene induced by ICSBP and IFN alpha and also a requirement in the expression of ICSBP in BCR-ABL transformed cells to generate an anti-leukemic immune protection via experimentation. CCL6 and CCL9 were overexpressed in BaF3 cells and injected with BCR-ABL into syngeneic mice. Although the mice still developed leukemia, it delayed the advancement of the disease by several weeks proving that CCL6 and CCL9 contribute to the creation of an anti-leukemic response within infected cells.

References

Cytokines {{protein-stub