Granulocyte macrophage colony-stimulating factor

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Not to be confused with granulocyte colony-stimulating factor.


Granulocyte macrophage colony-stimulating factor
Systematic (IUPAC) name
Human granulocyte macrophage colony stimulating factor
Identifiers
CAS number	83869-56-1
ATC code	L03AA09
PubChem	?
DrugBank	BTD00035
Chemical data
Formula	C₆₃₉H₁₀₀₆N₁₆₈O₁₉₆S₈
Mol. mass	14434.5 g/mol
Pharmacokinetic data
Bioavailability	?
Metabolism	?
Half life	?
Excretion	?
Therapeutic considerations
Pregnancy cat.	?
Legal status
Routes	?

colony stimulating factor 2 (granulocyte-macrophage)
Identifiers
Symbol	CSF2
HUGO	2434
Entrez	1437
OMIM	138960
RefSeq	NM_000758
UniProt	P04141
Other data
Locus	Chr. 5 q23-q31

Granulocyte-macrophage colony-stimulating factor, often abbreviated to GM-CSF, is a protein secreted by macrophages, T cells, mast cells, endothelial cells and fibroblasts.

1 Functions
2 Glycosylation
3 Clinical significance
- 3.1 Leukine
- 3.2 Controversy
4 References
5 External links

[edit] Functions

GM-CSF is a cytokine that functions as a white blood cell growth factor. GM-CSF stimulates stem cells to produce granulocytes (neutrophils, eosinophils, and basophils) and monocytes. Monocytes exit the circulation and migrate into tissue, where upon they mature into macrophages. It is thus part of the immune/inflammatory cascade, whereby activation of a small number of macrophages can rapidly lead to an increase in their numbers, a process crucial for fighting infection.

[edit] Glycosylation

Human granulocyte macrophage colony-stimulating factor is glycosylated in its mature form. The glycosylation sites are reported to be at amino acid residues 23 (leucine), 27 (asparagine), and 39 (glutamic acid) (see US Patent No. 5,073,627).^[1]

[edit] Clinical significance

GM-CSF is also known as molgramostim or, when the protein is expressed in yeast cells, sargramostim (Leukine®). GM-CSF is used as a medication to stimulate the production of white blood cells following chemotherapy.

[edit] Leukine

Leukine is the trade name of sargramostim manufactured by Berlex Laboratories, a subsidiary of Schering AG. Its use was approved by U.S. Food and Drug Administration for acceleration of white blood cell recovery following autologous bone marrow transplantation in patients with non-Hodgkin's lymphoma, acute lymphocytic leukemia, or Hodgkin's disease in March 1991.^[2] In November 1996, the FDA also approved sargramostim for treatment of fungal infections and replenishment of white blood cells following chemotherapy.^[3]

[edit] Controversy

Berlex funded a study that ran in the May 26, 2005 issue of the New England Journal of Medicine which concluded that, although GM-CSF did not produce remissions in Crohn's disease, it did decrease disease severity and improve quality of life.^[4]

The study's lead author, Joshua Korzenik of Harvard Medical School and Massachusetts General Hospital, is a paid consultant for Berlex , and co-owns the patent on the drug.^[5] Korzenik created a "firewall" to protect the integrity of the study, consisting of two committees to review the study results and process as well and sending trial data to outside clinicians for review.^[5]

[edit] References

^ http://www.google.com/patents?vid=USPAT5073627&dq=5,073,627
^ [1] Details of Approved Claims by Line of Therapy, Approved Claims for 1991, FDA.gov
^ [2] Drugs Approved by the FDA, Drug Name: Leukine (sargramostim), CenterWatch.com
^ Korzenik J, Dieckgraefe B, Valentine J, Hausman D, Gilbert M (2005). "Sargramostim for active Crohn's disease". N Engl J Med 352 (21): 2193-201. PMID 15917384.
^ ^a ^b "Med school drug pushers: How scientists are selling out to drug companies", by David S. Bernstein, The Phoenix. Published April 12, 2006. Accessed 8 Feb 2007.