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Alert Number 199

Familial CLL: New Developments

Date: November 13, 2006

Familial CLL is a topic that is close to my heart, and if you are a parent or grandparent, I expect it is close to yours as well.

There is little doubt that there are examples of CLL striking several times within the same family. While this is a double or triple tragedy to the families involved, it gives us an important window into the inner workings of the disease. If we get a better handle on the genetic and inheritable underpinnings of CLL, it may be easier to monitor for it, control it with smarter therapies, and ultimately cure it. CLL Topics has urged all family clusters to register their cases with the researchers studying this aspect of CLL. By doing that you will be helping yourselves as well as helping others that are the victims of this awful disease. Here are links to our prior articles on the subject.

Not the Worst Day of Your Life;
Familial CLL: Mayo Clinic Perspective.

The latest issue of "Blood" has an interesting article on the subject (see abstract below). The authors claim that they have identified a novel candidate gene on the 13th chromosome that may predispose to familial CLL. I asked Dr. Tim Call of Mayo Clinic to comment on this paper. His response is that they have been collaborating with the group doing this research, and this particular area of the 13th chromosome has been of significant interest. They need validation of these exciting but preliminary findings by checking things out with larger groups of patients. Stay tuned, and if you are a member of a family group that has more than one case of CLL, please, please, do register your case with Mayo Clinic or the NCI. Here is the contact information.

The Genetic Epidemiology Branch of the National Cancer Institute has a program for collecting blood and family histories on familial CLL families. Information can be obtained by calling 1-800-518-8474.

Mayo Clinic, Rochester, MN has a research study for families with either CLL or lymphoma. Individuals can either be seen at the clinic, or can fill out questionnaires and submit blood samples from their home facility. Information can be obtained by calling 1-800-610-7093.

Be well,

Chaya
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Abstract

Blood. 2006 Oct 17.

Identification of a novel chromosome region 13q21.33-q22.2 for susceptibility genes in familial chronic lymphocytic leukemia.

Ng D, Toure O, Wei MH, Arthur DC, Abbasi F, Fontaine L, Marti GE, Fraumeni Jr JF, Goldin LR, Caporaso N, Toro JR.

Genetic Epidemiology Branch, Division of Cancer Epidemiology & Genetics, National Cancer Institute, NIH, DHHS, Rockville, MD.

Chronic lymphocytic leukemia (CLL) is the most prevalent form of leukemia in adults in western countries. A genome scan of CLL-prone families found a lod score of one in band 13q22.1. To investigate this finding, we selected six CLL families consisting of 65 individuals (CLL affected n=19, unaffected n=46) for genotyping and fine mapped a 23 megabase region in 13q14.2-q22.2. Interphase FISH revealed 13q14 deletion in 85% (11/13) of CLL patients. Four CLL families shared a 3.68 Mb minimal region in 13q21.33-q22.2. Two asymptomatic siblings who shared the 13q21.33-q22.2 at risk haplotype exhibited CD5+ monoclonal B-cell lymphocytosis (MBL) on flow cytometry. One of these individuals also had 13q14 deletion by FISH. These two MBL individuals shared the at risk haplotype with their CLL affected relatives providing further evidence of the relationship between CLL and MBL, and the biologic significance of this novel region. Using direct DNA sequencing analysis we screened 13 genes for germline mutations but no frameshift or nonsense mutations were detected. Our studies revealed that 11 of the 13 genes in the candidate region were expressed in immune tissues supporting that they have functional relevance in investigations of familial CLL. In conclusion, we identified a novel candidate region that may predispose to familial CLL.

PMID: 17047154
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