There are a lot of BCL genes - at least 10 that I know of. BCL-1 is involved in mantle cell lymphoma and BCL-2 in follicular lymphoma. BCL-3 is associated mainly with a rather rare type of CLL.
A paper published in Brit J Haematol (Rossi et al 2010; 150:702-4) brings us up to date on the subject. Several short series of case reports have identified that these cases with the t(14;19) translocation as being CLL with atypical morphology, tending not to express CD23, having a low Matutes score, being associated with trisomy 12, unmutated IGHV genes, and biased usage of IGHV4-39. There has also been a suggestion that such cases are more likely to transform to Richter's disease, but this has not been substantiated.
Rossi and colleagues have estimated the incidence of bcl-3 translocations as 1.8% of cases of CLL. It is almost always associated with trisomy 12 occurring in about 10% of trisomy 12 cases.
I have always thought that trisomy 12 CLL is a stand alone category of CLL. We have written in the past about the association of trisomy 12 and atypical CLL (Trisomy 12 defines a group of CLL with atypical morphology: correlation between cytogenetic, clinical and laboratory features in 544 patients. Matutes E, Oscier D, Garcia-Marco-J, Ellis J, Copplestone A, Gillingham R, Hamblin T, Lens D, Swansbury GJ, Catovsky D. Brit J Haem 1996 92: 382-8) and it is a fact that the gain of del 11q and del 17p are not trisomy 12 features. The surface Ig tends to be bright and so do CD20 and FMC7, and there are more prolymphocytes around tan you would expect.
So the interesting question is whether also having a bcl-3 translocation makes matters worse. Rossi et al have looked at this and the answer seems to be no. Treatment-free survival, overall survival and Richter's transformation were no worse fro the 10% of trisomy 12s that had the t(14;19) translocation than for the 90% who didn't. Of course the numbers are small and some difference might appear with a larger series, but the other point is that very occasionally a bcl-3 translocation appears without trisomy 12 and with normal morphology and markers. These cases behave benignly which makes me think that it is the trisomy wot done it.
Incidentally age, sex, stage, lymphocyte count, splenomegaly, lymph node enlargement, CD38 or Zap-70 were none of them associated with the acquisition of bcl-3 translocations. Only IGHV4-39 in its unmutated form.
2 comments:
Thanks for this. Very helpful. Seems the drugs that block specific pathways big and small -PI3. SYK, BCR, and so on are getting much attention in CLL as the possible hope for a non-toxic oral treatment to keep the CLL under control. I wonder what your take is?
Keeping a watching brief on this. I think Dr Furman is the source of most information.
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