Deletion 20q in CLL May Represent Disease Progression

Lynne V. Abruzzo, MD, PhD

The identification of a deletion 20q (del[20q]) in a patient with chronic lymphocytic leukemia (CLL) may not indicate they have developed a myelodysplastic syndrome (MDS) as was previously assumed, according to new research published in Modern Pathology.

Researchers at The University of Texas MD Anderson Cancer Center found that in cases with morphologic evidence of dysplasia, del(20q) likely resides in the myeloid lineage. However, in cases without morphologic evidence of dysplasia, del(20q) may represent clonal evolution and disease progression in CLL.

It was determined that among 64 patients with CLL, del(20q) was the sole abnormality in 40 cases, a stemline abnormality in 21, and a secondary abnormality in 3. FISH analysis revealed an additional high-risk abnormality, del(11q) or del(17p), in 39% of cases.

To better understand how this discovery may change patient management, OncLive spoke with one of the study’s authors, Lynne V. Abruzzo, MD, PhD. Abruzzo worked at MD Anderson Cancer Center at the time the research was conducted and is currently a professor of Pathology/Clinical Pathology at Ohio State University Compressive Cancer Center.

OncLive: How was it determined that del(20q) could be present in some CLL patients but not be indicative of MDS?

Dr Abruzzo: When studying leukemia and lymphoma, one of the things that we do is grow the cells in culture. After they divide, we then prepare slides and look at the chromosomes. By looking at the chromosomes in many cancers, particularly leukemia, we can find certain abnormalities. These abnormalities give us a very good idea of what the disease is.

For example, patients with chronic myeloid leukemia (CML) have a translocation between a specific part of chromosome 9 and a specific part of chromosome 22. If we see that when we are looking at the chromosomes, and combine that with other information, we can make a diagnosis of CML. There are other chromosome abnormalities that we commonly see in certain kinds of acute leukemia.

In CLL, the disease that I study, there is no single genetic abnormality, but there is a couple of abnormalities that we see commonly. Del(20q) is not one of them. Every person has 22 pairs of autosomes and then a pair of sex chromosomes. Loss of part of the chromosome 20 is often seen in MDS. For many patients with MDS, their bone marrow eventually fails and they stop making blood cells or they go on to develop a more acute leukemia. Del(20q) is an abnormality that we tend to see in MDS, but we don’t think of it as being associated with CLL.

One thing to keep in mind is, if you look at the demographics, most patients who are diagnosed with CLL are older adults. Most patients who get MDS are also older adults. Why do people get CLL? We don’t really know. Why do people get MDS? We don’t know, but we do have some idea of a cause in some cases. We do know that patients who have received certain types of chemotherapy for one cancer are more likely to develop MDS.

In this trial, we had patients who had all been treated for CLL. When they returned for testing, it was discovered that they had a del(20q). What does that mean? The obvious assumption would be that they acquired MDS due to chemotherapy exposure or age, in addition to CLL.

However, when looking at the bone marrow of these patients, I noticed that, in several of them, their bone marrow was so overrun with CLL that there was no way we could be getting the abnormal karyotypes from the MDS cells. In those cases, I could not identify any MDS cells. The question became, “Could this del(20q) be in their CLL cells, in which they do not have MDS, but a new abnormality that we generally don’t expect?”

We took the cells, made smears, and did FISH, which allows us to look at the chromosomes in the nuclei of the cell. When we look at the cells, we can tell if they are MDS or CLL cells. In about half of the cases, we found that the abnormality was in the MDS cells, as expected, but in the other half of the cases, it was actually in the CLL cells.

Why is this discovery significant?

If you had an older patient who you were treating for CLL, and you studied their chromosomes and you found a del(20q) abnormality, the assumption you would make, as a physician, is that the patient is now developing MDS. What we showed is that you can also see this abnormality in CLL cells, which is a more accurate diagnosis for the patient. The wrong diagnosis may impact the patient’s prognosis. We haven’t followed these patients long enough to know, but it is generally easier to treat CLL than it is MDS. Usually, physicians will not administer treatment based on an abnormal karyotype. They will wait and see if other symptoms develop. However, if a person has del(20q) and similar symptoms that do develop in MDS, they still may not have MDS. You would want to make sure that the person receives treatment for CLL and you are not just watching and waiting to see what happens, assuming they have MDS. This could lead to better treatment.

Why do you think it was not determined earlier that CLL patients could exhibit del(20q) in this manner?

There are very rare cases, maybe six, of del(20q) being reported in patients with CLL. It is an unusual abnormality to begin with. However, larger cancer centers, like MD Anderson and Ohio State, see hundreds patients with CLL annually. This allows us to identify these rare abnormalities. The average hematologist in private practice is probably never going to see this. However, one of the things that can happen with these abnormalities is that once someone describes it, more people are on the lookout for it.

Many people also never receive treatment for CLL because the disease is not going to harm them. Those people are never going to have a karyotype done. It is only the people that go to a cancer center or a university hospital where they are going to do this type of testing. I would not want all patients with CLL to have testing done for del(20q) if they are not receiving treatment. It is very rare.

What are the next steps in this research?

One of the questions we want to answer is, “What genes are involved?” Our data suggests that patients with CLL who develop a del(20q) have more aggressive disease. However, I would never say that to a patient because our numbers are so small. Most clinicians are not going to karyotype patients with CLL. If we see a del(20q), that does not always mean the patient is going to do poorly. The point is for the hematologist to be aware and not make assumptions that this is MDS. This could be CLL and the patient may need to have their CLL treated.