what type of mutation produces the bcr-abl chimeric protein
retrotransposition tandem duplication chromosomal translocation
translocation, tandem duplication, or retrotransposition creates a novel coding sequence containing parts of the coding sequences from two different genes. Naturally occurring fusion proteins are commonly found in cancer cells, where they may function as oncoproteins. The bcr-abl fusion protein is a well-known example of an oncogenic fusion protein, and is considered to be the primary oncogenic driver of chronic myelogenous leukemia. Some fusion proteins combine whole peptides and therefore contain all functional domains of the original proteins. However, other fusion proteins, especially those that occur naturally, combine only portions of coding sequences and therefore do not maintain the original
Fusion protein
with cancers such as Ewing’s sarcoma, melanoma, and breast cancer. In chronic myeloid leukemia (CML), NOV is downregulated as a consequence of the kinase activity of BCR-ABL, a chimeric protein generated through the chromosomal translocation between chromosome 9 and 22. Forced expression of NOV inhibits proliferation and restores growth control in CML cells, suggesting that NOV may be an alternate target for novel therapeutics against CML. NOV (gene) NOV (nephroblastoma overexpressed) also known as CCN3 is a matricellular protein that in humans is encoded by the "NOV" gene. NOV is a member of the CCN family of secreted, extracellular matrix
NOV (gene)
suggesting an important role for CCL9 in bone resorption. CCL9 is constitutively expressed in macrophages and myeloid cells. The gene for CCL9 is located on chromosome 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 (CML). CML is a type of cancer in which the bone marrow produces too many red blood cells. This is caused by chromosomal translocation, a mutation in which the abnormal gene BCR-ABL, is turned into a CML cell. CML starts off as a myeloproliferative for example in
CCL9
9"), and a truncated chromosome 22 ("the Philadelphia chromosome, 22q-)." In agreement with the International System for Human Cytogenetic Nomenclature (ISCN), this chromosomal translocation is designated as t(9;22)(q34;q11). The symbol "ABL" is derived from Abelson, the name of a leukemia virus which carries a similar protein. The symbol BCR is derived from breakpoint cluster region, a gene which encodes a protein that acts as a guanine nucleotide exchange factor for Rho GTPase proteins. Translocation results in an oncogenic BCR-ABL gene fusion that can be found on the shorter derivative 22 chromosome. This gene encodes for a BCR-ABL fusion protein. Depending
Philadelphia chromosome
such as proliferation and survival. In a particular cancer, such a network may be radically altered, due to a chance somatic mutation. Targeted therapy inhibits the metabolic pathway that underlies that type of cancer's cell division. The classic example of targeted development is imatinib mesylate (Gleevec), a small molecule which inhibits a signaling molecule kinase. The genetic abnormality causing chronic myelogenous leukemia (CML) has been known for a long time to be a chromosomal translocation creating an abnormal fusion protein, kinase BCR-ABL, which signals aberrantly, leading to uncontrolled proliferation of the leukemia cells. Imatinib precisely inhibits this kinase. Unlike so
History of cancer chemotherapy
translocation, tandem duplication, or retrotransposition creates a novel coding sequence containing parts of the coding sequences from two different genes. Naturally occurring fusion proteins are commonly found in cancer cells, where they may function as oncoproteins. The bcr-abl fusion protein is a well-known example of an oncogenic fusion protein, and is considered to be the primary oncogenic driver of chronic myelogenous leukemia. Some fusion proteins combine whole peptides and therefore contain all functional domains of the original proteins. However, other fusion proteins, especially those that occur naturally, combine only portions of coding sequences and therefore do not maintain the original
Fusion protein
judge for the district court in Beauce. Arthur Godbout Arthur Godbout (December 13, 1872 – March 12, 1932) was a Canadian lawyer, politician, and judge. Born in Lambton, Quebec, Godbout studied at the Séminaire de Québec and the Université Laval à Montréal. He was called to the Bar of Quebec in 1898 and was created a King's Counsel in 1912. He was a lawyer in Saint-Georges-Est and Saint-Joseph. He was elected to the Legislative Assembly of Quebec for Beauce in a 1902 by-election. A Liberal, he was re-elected in 1908 and 1912. He was acclaimed in 1916 and re-elected in
Arthur Godbout
many platforms this includes: PSP, BMW Online, iDrive, Calendar plus, Windows Desktop RSS gadget, and Feeddler RSS Reader for iPad and iPhone. Mlpman is the eBay and Amazon operating name of MLPLIVE. It was formed on 17 July 2000. The record label owns and maintains the sub as well as control its logistics. From 1 January 2001, MLPMAN went worldwide. However, MLPMAN now rarely operates on Amazon as of Amazon offering the product under its own brand. The Mlplive.com shop opened in 2007 and allows customers to purchase CDs without going through either shops or Mlpman. The shop sells all
Major League Productions
widening a pre-existing natural karst. How the Israelite engineers dealt with the difficult feat of making two teams digging from opposite ends meet far underground is still not fully understood, but some suggest that the two teams were directed from above by sound signals generated by hammering on the solid rock through which the tunnelers were digging. The tunnel was first described in modern times by Franciscus Quaresmius in 1625. It was later explored in 1838 by the American biblical scholar Edward Robinson, and in 1865 by Charles Warren. Neither Quaresmius nor Robinson identified the tunnel with Hezekiah, but in
Siloam tunnel
contact with Alexander the Great. Tiridates realized the futility of trying to resist Alexander's forces, and so allowed Alexander to massacre Ariobarzanes and his troops right outside the city walls of Persepolis rather than fight against Alexander. This is in agreement with Curtius' account which states that the Persian force, after both inflicting and suffering heavy casulties in the ensuing battle, broke through the Macedonian forces and retreated to Persepolis, but were denied entrance into the capital at which point they returned to fight Alexander's army to the death. A few historians regard the Battle of the Persian Gate as
Battle of the Persian Gate
eventual 2008 settlement was $15 million. In 1998, ISKCON published an exposé of widespread physical, emotional and sexual abuse of children in the group's boarding schools in the United States and India. The Hare Krishna monks and young devotees caring for the children had no training in the task and often resented having to perform it, the report said. At a meeting in 1996, former Krishna pupils testified that they had been regularly beaten at school, denied medical care, and sexually molested and raped. The Child Protection Policy and Procedure Guidelines was revised and ratified by the GBC in June
International Society for Krishna Consciousness
molecules that inhibit the fusion oncoprotein AML1-ETO. Therefore, in terms of M2 subtype acute myeloid leukemia, the most prominent target is the abnormal AML1-ETO fusion protein. Similarly, chronic myeloid leukemia (CML) is comparable to acute myeloid leukemia M2 because it also forms a fusion oncoprotein – BCR-Abl. The developed tyrosine kinase inhibitor, imatinib mesylate, has had a tremendous effect on stopping cancer progression in the majority of chronic myeloid leukemia patients. BCR-Abl is constitutively active due chromosome translocation; therefore it over-phosphorylates the tyrosine kinase. Imatinib mesylate works to block BCR-Abl’s activity by blocking the active kinase domain (Fava et al.,
Acute myeloblastic leukemia with maturation
gene. RUNX1T1 has been shown to interact with: RUNX1T1 Protein CBFA2T1 is a protein that in humans is encoded by the "RUNX1T1" gene. The protein encoded by this gene is a putative zinc finger transcription factor and oncoprotein. In acute myeloid leukemia, especially in the M2 subtype, the t(8;21)(q22;q22) translocation is one of the most frequent karyotypic abnormalities. The translocation produces a chimeric gene made up of the 5'-region of the RUNX1 gene fused to the 3'-region of this gene. The chimeric protein is thought to associate with the nuclear corepressor/histone deacetylase complex to block hematopoietic differentiation. Several transcript variants
RUNX1T1
possibilities, and was considered by Baltimore as of 2005 to be "our most significant discovery in immunology". In 1990, as a student in David Baltimore's laboratory at MIT, George Q. Daley demonstrated that a fusion protein called bcr-abl is sufficient to stimulate cell growth and cause chronic myelogenous leukemia (CML). This work helped to identify a class of proteins that become hyperactive in specific types of cancer cells. It helped to lay the groundwork for a new type of drug, attacking cancer at the genetic level: Brian Druker's development of the anti-cancer drug Imatinib (Gleevec), which deactivates bcr-abl proteins. Gleevec
David Baltimore
a specific inhibitor of a number of tyrosine kinase enzymes. It occupies the "TK" active site, leading to a decrease in activity. There are a large number of "TK" enzymes in the body, including the insulin receptor. Imatinib is specific for the "TK" domain in "abl" (the Abelson proto-oncogene), c-kit and PDGF-R (platelet-derived growth factor receptor). In chronic myelogenous leukemia, the Philadelphia chromosome leads to a fusion protein of "abl" with "bcr" ("breakpoint cluster region"), termed "bcr-abl". As this is now a constitutively active tyrosine kinase, imatinib is used to decrease "bcr-abl" activity. The active sites of tyrosine kinases each
Imatinib
of the BCR protein. Although the BCR region also expresses serine/threonine kinases, the tyrosine kinase function is very relevant for drug therapy. As the N-terminal Y177 and CC domains from BCR encode the constitutive activation of the ABL1 kinase, these regions are targeted in therapies to downregulate BCR-ABL kinase activity. Tyrosine kinase inhibitors specific to such domains as CC, Y177, and Rho (such as imatinib and sunitinib) are important drugs against a variety of cancers including CML, renal cell carcinoma (RCC) and gastrointestinal stromal tumors (GISTs). The fused "BCR-ABL" protein interacts with the interleukin-3 receptor beta(c) subunit and is moderated
Philadelphia chromosome
retrotransposition tandem duplication chromosomal translocation
Title: Fusion protein. Content: translocation, tandem duplication, or retrotransposition creates a novel coding sequence containing parts of the coding sequences from two different genes. Naturally occurring fusion proteins are commonly found in cancer cells, where they may function as oncoproteins. The bcr-abl fusion protein is a well-known example of an oncogenic fusion protein, and is considered to be the primary oncogenic driver of chronic myelogenous leukemia. Some fusion proteins combine whole peptides and therefore contain all functional domains of the original proteins. However, other fusion proteins, especially those that occur naturally, combine only portions of coding sequences and therefore do not maintain the original
Chromosomal translocation
Chromosomal translocation
The bcr-abl chimeric protein is produced by a chromosomal abnormality that results in the formation of a so-called Philadelphia chromosome. This abnormality is a consequence of fusion between the Abelson (Abl) tyrosine kinase gene at chromosome 9 and the break point cluster (Bcr) gene at chromosome 22, resulting in a chimeric oncogene (Bcr-Abl). The mutation is a translocation between chromosomes 22 and 9. So the answer
chromosomal translocation
The bcr-abl chimeric protein is produced by a chromosomal abnormality that results in the formation of a so-called Philadelphia chromosome. This abnormality is a consequence of fusion between the Abelson (Abl) tyrosine kinase gene at chromosome 9 and the break point cluster (Bcr) gene at chromosome 22, resulting in a chimeric oncogene (Bcr-Abl). The mutation is a translocation between chromosomes 22 and 9. So the answer
chromosomal translocation