Chronic lymphocytic leukemiassmall cell lymphoma

Chronic lymphocytic leukemia is a low-grade lymphoma marked by a peripheral lymphocytosis of CD5+, CD20+, CD23+ small lymphocytes that are similar in morphology to normal lymphocytes. BCL-2, which is expressed at low levels in normal lymphocytes, is expressed at high levels in more than 70% of CLL cases but this is rarely, if ever, due to a t(14;18). Staging based on presence of lymphadenopa-thy, organomegaly anemia or thrombocytopenia can provide prognostic information, those in the best prognostic groups enjoying normal mean survival times.

Prognosis can also be estimated by purely molecular criteria. In about half of CLL cases, lymphocytes are CD38+, IgD-, and contain VH genes which exhibit somatic hypermutation. In the other half of CLL cases, the malignant lymphocytes resemble naive B cells, with surface marking CD38-, IgD+, and they lack VH mutations. CLL with immunoglobulin VH genes that exhibit more than 2% somatic hypermutation has significantly better survival than the latter.

Table 10.3 Abnormal genes in CLL.



Median survival (months)

13q deletion



11q deletion



12 trisomy



17p deletion



Normal karyotype



Other B-cell malignancies are characterized by chromosomal translocations, but there are no chromosomal translocations that characterize a significant subset of CLL. There are, however, several important genetic abnormalities in the absence of translocations. Whereas conventional Giemsa-trypsin banding analysis of chromosomes from CLL cells detected cytogenetic abnormalities in about half of CLL cases, the higher sensitivity of FISH has allowed the detection of genomic aberrations in 82% of cases. As FISH is a directed rather than a screening technique, these abnormalities had previously been demonstrated by conventional banding techniques. The abnormalities include del 13q (50%), del 11q (18%), +12q (16%), del 17p (7%) and del 6q (7%) (Table 10.3). Regression analysis allowed the assignment of 90% of these cases to one of five prognostic classes based on genetic abnormalities. The best prognostic group included those that had 13q deletion as their sole abnormality, with a median survival of 133 months. The worst prognostic group contained those with a 17p deletion, with a mean survival of 32 months. CLL with 17p and 11q deletions were more likely to have extensive lymphadenopathy, splenomegaly, cytopenias, and B symptoms. Examples of chromosome 13 and trisomy 12 detected by FISH and by CGH microarray are shown in Plates 10.3 and 10.4 respectively. These data raise the question of whether the classical clinical staging, which can be used to predict survival, is partly just a surrogate for particular genetic abnormalities, and it is the genetic abnormalities and resulting expression patterns that are more important in determining prognosis.

The specific genes affected by these abnormalities that are important for CLL oncogenesis are not known. The critical tumor suppressor lost in the 13q deletion is probably not RB, but rather a gene that lies telomeric and has so far defied definitive identification. Tumor suppressor p53 is involved in 17p deletions. Overall, p53 abnormalities have been found in at least 15% of patients, and are associated with an increased percentage of prolymphocytes and a poorer outcome.

10 Ways To Fight Off Cancer

10 Ways To Fight Off Cancer

Learning About 10 Ways Fight Off Cancer Can Have Amazing Benefits For Your Life The Best Tips On How To Keep This Killer At Bay Discovering that you or a loved one has cancer can be utterly terrifying. All the same, once you comprehend the causes of cancer and learn how to reverse those causes, you or your loved one may have more than a fighting chance of beating out cancer.

Get My Free Ebook

Post a comment