Genetic deletions in CLL

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Published: 9 Sep 2015
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Dr Carlo Croce - The Ohio State University College of Medicine, Columbus, USA

Professor Carlo Croce speaks to ecancertv at the 2015 International Workshop on Chronic Lymphocytic Leukaemia (CLL) about studies on genetic deletions in the pathogenesis of CLL.

Genetic deletions in CLL

Dr Carlo Croce - The Ohio State University College of Medicine, Columbus, USA


What I am trying to do is to find out which are the genetic changes that cause chronic lymphocytic leukaemia and on that basis offer to develop treatments which are much better than the treatments which are available now. So that’s the bottom line.

In the case of CLL we have discovered some time ago the most common genetic alteration in chronic lymphocytic leukaemia. On that basis we can make some predictions about what might be the best treatment for CLL. Essentially what we discovered some time ago was that the most common genetic alteration in chronic lymphocytic leukaemia is a loss of two microRNAs which are on chromosome 13, which are included [?? 1:09] on chromosome 13. When these two microRNAs are lost we found a target of those microRNAs, which is the gene that we discovered in 1984 called Bcl-2, Bcl-2 seemed to be a great target for developing therapy against CLL. In fact, now there is a drug called ADT-199 which is a specific anti-Bcl-2 drug that shows some remarkable activity in the case of patients with CLL. But these two microRNAs also inhibit another anti-apoptotic gene of the Bcl-2 primary called Mcl-1. Today we don’t have anti-Mcl-1 therapy but one of these days we will. So if we will treat patients with CLL with an anti-Bcl-2 drug and an anti-Mcl-1 drug the probability of getting rid of all the cancer cells would be very high, very great again. So we strongly believe that in order to cure cancer, and leukaemia in particular, we have to figure out what are the critical genetic steps that cause the leukaemia. If we can develop treatment directed specifically to those alterations we might have a huge impact in the treatment of the disease with marginal side effects.

So what research are you planning to do in the next few years?

In the next few years I think that we will try to define better all the genetic steps which are involved because it’s not only a question of the initiation step. I think that we know what initiates CLL and so we know already what target could be useful. But we do not know too much about the genetic alterations that occur during the progression of the disease and probably it would be important to know all those alterations too. So that’s what we are doing now.

Talking about the conference, I know you’ve been on the organising committee, what do you think some of the highlights are and some of the really exciting findings?

You know, I am a little bit of a mutant in the committee because the committee is mainly formed by physicians, by people treating CLL. Instead, I am a fundamental scientist, I try to figure out what happens in CLL and what causes the disease so we are pretty complementary. I think that the progress in the understanding of CLL has been remarkable during this last 10-12 years and the treatments are improved quite remarkably. We can guarantee essentially significant survival to patients with CLL, even this aggressive form of CLL. What we want to do is to cure the disease and I think that one of these days we will. We are on the good track.