Re: [CML] Live from ASH!

[Jerry Mayfield]

Brett,   Here is a patient report back from ASK which mentions the new drug for T315I.....SGX67686A....Dr. Druker was reporting on it.   Jerry ----- Original Message ----- From: cher111376 To: [EMAIL PROTECTED] Sent: Friday, December 03, 2004 6:34 PM Subject: [CML] Live from ASH! Imatinib Mesylate: Broadening usage and the issue of resistance- Brian J. Druker This afternoon's session was really neat because we got to hear and see Dr. Druker give this talk.  It was sponsored by the LLS. We gained a new respect for Dr. Druker because he changed and updated his talk in order to bring more information on the special areas of resistance and mutations mechanism, which is of great interest at this conference.   We definitely got more of an insight into the three dimensional issues of mutations and how they can affect the ability of IM to bind and do its work. On a variation of Dr. Hughes data, Dr. D. said he put the disease load of PCRU at 106 versus Dr. H. 10 5.  By comparison, there are 10 ^11 peripheral blood cells in the human body.    55% of CML patients will achieve a 3 log reduction and there is less than a 2% chance of relapse per year in this patient group, versus 4% as an average of all CML patients. Potential mechanism of molecular persistence If BCR ABL is being inhibited then some resistant mechanisms could be: -Stem cell quiescent issues -Kinase independent that affects BCR abl (other inhibitors than gleevec) If BCR ABL is not being inhibited then some resistant mechanism could be: -Drug efflux -Kinase domain mutation -BCR amplification/Overexpression This helped us to fill in some of the blanks from this mornings talk. Of the kinase domain mutations Dr. D. outlined three mechanisms 1.)      direct binding 2.)      p-loop mutation 3.)      effects from direct conformation The shape shifting ability of some of these mutations doesn't necessarily preclude that IM will not work; it just may mean you need more of IM to get the job done.  In a sense it makes it more difficult for the molecules to connect, so you try to give it more opportunity by increasing the dose. The BMS drug inhibited all mutations except T315I and AMN107 inhibited most, with the caveat that the dose may be dependent on the type of mutation. HEADS UP � GOOD NEWS Leave it to Dr. D. to bring us good news in all of this, there is a new drug in predevelopment clinical phase that will specifically target T315I!!!! � Happy Bodhi day, Merry Christmas, Happy Hanukkah, Happy Yule, Merry Kwanza, and we hope we are not forgetting anyone.  It is called SGX67686A from GenomiX He also said that IM is showing positive effect in a greater number of diseases, aside from CML and GIST, HES, subset of CMML patients who express EVT6 and rare AML patients who express EVT6 abl, lastly patients with dermatofibrosarcoma protuberans (DFSP) (17.22 chromosomes changes) and ALL patients that are BCR ABL patients (albeit transient in this last one). Your friendly internet ASH reporters live from a "hot spot" at the "it's a grind" coffee shop. Cheryl-Anne and Mark New! Sign up for local CML support group meetings in your local community at http://cml.meetup.com Apply for Commercial Real Estate loans online and submit your deal to dozens of hungry lenders in just minutes. Loan programs for all types of business and commercial real estate. Apply anytime at http://realestatezoo.com CML (Chronic Myelogenous Leukemia Support List) --------------------------------- Part Of CMLHope.Com An International Community Of CML Patients For more information: http://cmlhope.com Post Message: [EMAIL PROTECTED] Subscribe:  [EMAIL PROTECTED] Unsubscribe:  [EMAIL PROTECTED] Change To No Mail/Web: [EMAIL PROTECTED] Change To Digest: [EMAIL PROTECTED] Change To Email: [EMAIL PROTECTED] List Help: [EMAIL PROTECTED]  CML Group Web Site http://groups.yahoo.com/group/CML New! Sign up for local CML support group meetings in your local community at http://cml.meetup.com Apply for Commercial Real Estate loans online and submit your deal to dozens of hungry lenders in just minutes. Loan programs for all types of business and commercial real estate. Apply anytime at http://realestatezoo.com CML (Chronic Myelogenous Leukemia Support List) --------------------------------- Part Of CMLHope.Com An International Community Of CML Patients For more information: http://cmlhope.com Post Message: [EMAIL PROTECTED] Subscribe:  [EMAIL PROTECTED] Unsubscribe:  [EMAIL PROTECTED] Change To No Mail/Web: [EMAIL PROTECTED] Change To Digest: [EMAIL PROTECTED] Change To Email: [EMAIL PROTECTED] List Help: [EMAIL PROTECTED]  CML Group Web Site http://groups.yahoo.com/group/CML Yahoo! Groups Sponsor ADVERTISEMENT Yahoo! Groups Links To visit your group on the web, go to: http://groups.yahoo.com/group/CML/   To unsubscribe from this group, send an email to: [EMAIL PROTECTED]   Your use of Yahoo! Groups is subject to the Yahoo! Terms of Service.