Q. I have a question about the Philadelphia chromosome. The Philadelphia chromosome is present in chronic myeloid leukemia. It’s also present in some case of precursor-B acute lymphoblastic leukemia. I guess I am assuming that the translocation will result in a similar gene product, but just in a different cell line. You mentioned that the Ph+ B-ALL in adults is a bad prognosis. I am wondering if this malignancy would be treated with imatinib, like CML, due to the drug targeting the specific protein that is formed (bcr-abl). If so, would there still be a bad prognosis? Thanks!
A. Great question! You are correct: a t(9;22) translocation involving the bcr and abl genes occurs in both CML and rare cases of precursor-B ALL. In some of the cases of Ph+ ALL, the genetic mutation (and gene product) is exactly the same as it is in CML; in others the breakpoint is slightly different, and a slightly different fusion protein is produced (but it is still a mutant tyrosine kinase with presumably similar effects on the malignant cells). Most cases of Ph+ ALL occurring in children have this different fusion protein, whereas only half of the cases occurring in adults have this different fusion protein (the other half of the adult cases have exactly the same breakpoint and product as is present in CML). It doesn’t seem to have any effect on prognosis whether you have the same fusion protein as in CML or the slightly different one.
You’re also correct that the genetic mutation occurs in different cell lines in each disease: in CML it is in the myeloid cell line, whereas in Ph+ ALL it is in the lymphoid cell line. One weird thing, though, is that in CML you can often find the Ph’ in lymphoid cells too. Strange. It indicates that the translocation between 9 and 22 occurs way back in a very early precursor stem cell, one that has not yet committed itself to the myeloid or lymphoid lineage. The occasional appearance of lymphoid blast crisis in CML indicates the same thing. We don’t see a similar picture in Ph+ ALL, though (there is no phase of the disease that involves myeloid cells). So perhaps in Ph+ ALL the translocation occurs in a lymphoid stem cell.
As for the treatment, it appears that imatinib is useful in Ph+ ALL. It doesn’t appear to get the patients into a long-term remission like it does in CML, unfortunately. But it does help get the patient into at least a first remission so that they can go on to bone marrow transplant (the official way to say this is that it improves early event-free survival). So the prognosis has improved somewhat for Ph+ ALL – but the outcome is nothing like the miraculous outcome in CML. Prognosis for Ph+ ALL is still very poor, both for kids and adults – in fact, Ph+ ALL has the worst prognosis of all the types of ALL.
Thank you for the information , but I’m curious . What about a pt that has both PH+ALL and PH+CML . 47 yr old male. CML in remission for 2 yrs . ALL active currently receiving chemo. The ALL is only showing in his spinal fluid . Any input would be appreciated .
Sounds to me like blast crisis CML. CML has three stages: chronic phase, accelerated phase and blast crisis. Blast crisis is basically an acute leukemia; it can be myeloid or lymphoid.
Hi. I have or had ALL ph+ , I have been taking imatinib for 14 years. My last 3 FISH for BCR/ABL studies didn´t showed any cell with the mutation. So I think imatinib is working great for me. =0)
WOW, Luisa, that’s GREAT!!! So happy for you! I would say “had” at this point 🙂
hello, this is a very interesting topic
i wonder why is ph+ve CML is much better prognosis than ALL ph+ve
Hi Nada – I think it is due to the nature of each of the diseases. CML is a chronic leukemia which typically progresses slowly (and now there is imatinib, so the prognosis is even better than it used to be). ALL is an acute leukemia, which means that it progresses quickly without treatment. Ph positive ALL has a worse prognosis in adults than it does in children. Children seem to respond better to the current chemo regimen, and often achieve a cure. The fact that they have the same chromosomal translocation doesn’t really alter the disease process in either CML or ALL, in terms of chronic vs. acute. The breakpoint is also different, which may or may not play a role.
Hi my name is Karen. I have cml with pH+.. my question is what is or does the pH+ mean or do? Is it on extra of the cml or does it go hand and hand? I’m just not clear on that. Thank you so much for your input on this.
Karen
Hi Karen – All cases of CML have the Philadelphia chromosome. It’s actually the cause of the disease – so it is present in every case. It’s a genetic mutation in the tumor cells that makes them grow faster. Fortunately, there’s now a great drug (imatinib, or Gleevec) that works on that exact genetic mutation. Please let me know if you have any other questions. All my best to you.
Hi just wondering if a diagnosis of ALL is the underlying diagnosis of CML? There is the Philadelphia chromosome present just wondering if CML was missed or if ALL can also carry that gene? This is in a child and what is the prognosis? Is the new drug Imatinib or gleevec available in Australia?
ALL and CML are totally different diseases – but you’re right, the Philadelphia chromosome can be present in both diseases. In CML, the Philadelphia chromosome is always present; in ALL, it is present only in some cases. The translocation is the same – t(9;22) – but the actual breakpoint is different in the two diseases. The genetics laboratory can detect which breakpoint is present, and that information should be included in the genetics report.
Finally, a couple things about CML and ALL. CML almost always occurs in adults, and ALL is most common in children (though it can occur in adults too). And the morphology (the way the bone marrow and blood look) is totally different in the two diseases. So it’s unlikely that one disease would be misdiagnosed as the other.
I would assume Imatinib is available in Australia…but ask your doctor to verify that.
Best of luck to you 🙂