News Article:
Drug Week. 2006, April 21. Acute Myeloid Leukemia Patients with KIT-D816 mutations linked to poor prognosis. Expanding Reporting; pg. 34
Primary Scientific:
Schnittger, S. et all (2006). KIT-D816 Mutations in AML1-ETO-Postive AML are associated with impaired event-free and overall survival
L, Eric. et all (2006)Efficacy and Safety of Gemtuzumab Ozogamicin in Patients With CD33-Positive Acute Myeloid Leukemia in First Relapse. Journal of Clinical Oncology, Vol 19, Issue 13, 2001: 3244-3254
Gabert, J., et all. (2003). Standardization and quality control studies of 'real-time' quantitative reverse transcriptase polymerase chain reaction of fusion gene transcripts for residual disease detection in leukemia – A Europe Against Cancer Program. 17, 2318–2357. doi:10.1038/sj.leu.2403135
Leukemia is a well known cancer. It is a cancer that effects the blood or bone marrow that is produces adnormal cell proliferation in the white blood cells. Leukemia is known to be acute or chronic. This cancer is known to be a life threatening disease.
KIT is a proto-oncogene, which is a normal gene that appears in the regulation of a normal cell growth. It is also converted into an oncogene which causes cell proliferation of D816 which becomes the form of KIT-D816 in Leukemia. The mutations codon D816 of the KIT gene characterizes genetic alterations in the AML (Acute Myeloid Leukemia).
Researchers have randomly analyzed 1940 AML patients that were screened for KIT mutations in exon 17 of tyrosine kinase domain. The AML patients were known to have increasing relapse of white blood cell counts. Out of the 1940 patients that were screened, 33 patients were known to be positive for D816 mutations. Out of the 33 patients, 8 were known to have t(8;21) which is higher compared to subgroup without D816 mutations and also affecting the codon 816 of the KIT gene that was detected.
Once that study was done, they have found that these patients who were known to have KIT-D816 mutations had poor prognosis to AML1-ETO-postive AML and should receive better treatment workup. This should happen early in the stage once noticed. Nevertheless, they will receive a combination of chemotherapy with KIT PTK inhibitors.
In both articles used to write a summary, the information was almost the same. However, the primary was more helpful, however harder to understand. Also in the primary article, it went into more details of the mutations.
Questions in Mind:
1. Have patients died from this mutation?
2. Are there certain drugs that would restrain the mutation?
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1 comment:
I am interested in the post regarding kit mutations and AML
(myelogenous leukemias: leukemias of myeloid cells); kit is a receptor that has been found on stem cells: it would make sense that stem cells would have receptors for growth factors; Lindsey notes that 33 out of about 1900 patients with AML had tumors with activating mutations in kit; I wonder if this is a high percentage compared to other types of tumors? Do the researchers mention if this mutation is found in other tumors? I am asking because I know that activating mutations in kit are also associated with GIST, or gastrointestinal stromal tumors. Will kit mutations start to be detected in other tumors? And what is the proposed mechanism of the kit contribution to these leukemias?
I was also interested in the fact that it was mentioned that the tumors with the activating kit mutations also had t(8;21), which if I remember correctly, is a transloaction of part of chromosome 8 to chromosome 21; translocations have been associated with other cancers (as well a severe genetic abnormalities in general); do the researchers talk at all about the significance of this genetic rearrangment that is seen more often in the tumors with the kit mutation? What genes are affected by this translocation?
intersting post!
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