The b2a2, b3a2, and e1a2 are three different types of the Philadelphia Chromosome, as defined by where they break off from chromosomes 9 and 22, and then re-attach at the wrong places. The Philadelphia Chromosome creates the BCR-ABL that our CML drugs inhibit. The report says you have at least 2 of the types, and possibly 3 -- I don't know why they combine the b2a2 and b3a2 into one report. If interested, you can ask the Onc if you have all 3 types. Overall, Gleevec can work against all 3 types of Philadelphia Chromosomes, but there are some issues associated with the e1a2. It is good news that the e1a2 is at extremely low levels. I have b2a2 and b3a2 and have done very well on Gleevec.
CML is caused by formation of the Philadelphia Chromosome.
http://atlasgenetics...s/t0922CML.html
People with CML can have various forms of BCR-ABL because the chromosomes can break off and re-attach (fuse) at different points. There are different types of BCR-ABL because when the pieces of chromosomes 9 and 22 break off and switch places (translocation) turning chromosome 22 into the leukemic Philadelphia chromosome, those pieces can break off at one on several locations along both the 9 and 22 chromosomes, which means they also fuse at different points. The locations are called a, b, c, e etc. Most CML is either b3a2 or b2a2 BCR-ABL and sometimes e1a2. In these the "b" is the BCR, and the "a" is the ABL. So if your #22 chromosome broke off at BCR exon #3 (b3), and your #9 chromosome broke off at ABL exon #2 (a2) then they combined to form BCR-ABL form b3a2, and so on. The b3a2 and b2a2 are the most prevalent forms of BCR-ABL and are found in p210 type CML. Some people have both b3a2 and b2a2 at the same time. Then there is the e1a2 BCR-ABL in p190 CML, which is more rare. So people with CML can have various forms of BCR-ABL because the chromosomes can break off and fuse at different points. There are also other even more rare types such as c3a2/e19a2 or e8a2 and other variants of BCR-ABL, and these probably require very close monitoring since less is known about them. Here is a chart on the various CML breakpoints:
http://jmd.amjpathol...full/6/4/343/F1
Here is another graphic showing the various breakpoints in CML:
http://www.bioscienc...791/figures.htm
(Note that the b2a2 and b3a2 were formerly called e13a2 and e14a2, as if we need more confusion)
http://www.cellsalive.com/pen.htm
Multiple breakpoints occurs in a small percentage of people with CML, and seems to have no real significance in terms of drug response.
But when determining your total level of BCR-ABL, you must add the PCR values for both variants together on each PCR. Here is some "light reading" on the subject of junction or breakpoint variants:
http://www.bloodjour...tract/92/9/3362
http://www.funpecrp....8_full_text.htm
http://www.pubmedcen...gi?artid=441382
Here is my blog collection of previous postings on the old L&LS Discussion Board, which contains more info under the sections listed below the link:
http://community.lls.org/blogs/CML
DIAGNOSIS
GENETICS OF CML
You may also want to read this previous posting:
http://community.lls.org/thread/3349?tstart=0
