[i-BCR (e19a2 junction)


230-kd protein (p230BCR-ABL)

In rare cases of CML, but in about 50 percent of adult Ph-positive ALL and in 80 percent of childhood Ph-positive ALL, the breakpoint on chromosome 22 is located 5' of M-bcr within a long intron segment between alternative exon e2' and e2 called the minor breakpoint cluster region (m-bcr) (Figure 4-2).24 Splicing out exons el' and e2' results in an e1a2 junction BCR-ABL transcript that is translated into a smaller BCR-ABL fusion protein of 190 kd (pi90BcR-ABL).25,26 Both p210BCR-ABL and pi90BCR-ABL display increased and constitutive tyrosine phosphokinase activity compared to the normal ABL protein p145ABL. A third breakpoint location (|-bcr) within BCR has been identified that is located 3' from M-bcr between exons e19 and e20 generating a fusion transcript with an e19a2 junction. The translation product is a protein of 230 kd (p230BCR-ABL) (Figure 4-2).27,28 Consistent but low-level coexpression of p190BCR-ABL with p210BCR-ABL has been demonstrated in most patients with CML in chronic phase.29 If present in comparable levels to p210BCR-ABL, pi90BCR-ABL disease may be characterized by a prominent monocytic component,30'31 whereas the subgroup of patients who expressed p230BCR-ABL has been associated with the neutrophilic leukemia variant, a lower white blood cell count than usually observed, and a slower progression to blast crisis (Table 4-1).27

About two-thirds of patients with CML express the reciprocal ABL-BCR fusion gene on the derivative chromosome 9q+. The 5' part of ABL exon lb is fused to the 3' tail of BCR exons b3 or b4. No pathogenetic role has been ascribed to ABL-BCR. Earlier reports of a correlation of ABL-BCR expression with a better response to treatment with interferon-alpha have not been confirmed.32

10 Ways To Fight Off Cancer

10 Ways To Fight Off Cancer

Learning About 10 Ways Fight Off Cancer Can Have Amazing Benefits For Your Life The Best Tips On How To Keep This Killer At Bay Discovering that you or a loved one has cancer can be utterly terrifying. All the same, once you comprehend the causes of cancer and learn how to reverse those causes, you or your loved one may have more than a fighting chance of beating out cancer.

Get My Free Ebook

Post a comment