Cytogenetics

The most important aspects of the cytogenetics of HCL are given in Table 29.8. Although many karyotypic abnormalities have been described,55 none are specific and none are consistently found in all HCL patients. Therefore, karyotypic analysis has not yet given any insight into the primary oncogenic event(s) responsible for the disease.

As pointed out by Basso et al.,4 HCs and CLL cells, unlike other malignant B cells, typically lack reciprocal balanced chromosomal translocations. Since these translocations are generated during Ig VDJ recombination, class switching and somatic hypermutation, their absence supports the proposition that both HCL and CLL are malignancies of mature memory B cells in which these processes are switched off.

HCL was the first hematological malignancy analyzed by comparative expressed sequence hybridization (CESH) to chromosomes.56 This showed a consistent expression profile of different chromosome regions that carry a "splenic signature," along with HC-specific under-or overexpressed regions.56 Moreover, these regions contained many genes which had also been found to be differentially expressed by gene-array

Table 29.8 Cytogenetics of HCL

• No consistent or specific cytogenetic abnormality

• Absence of translocations suggests malignant transformation of post-GC-type cells

• Most frequent recurrent abnormalities involve chromosomes 5(trisomy 5, 5q13 aberrations) and 14 (add (14)q(32) and del(14)(q)

• A range of other structural and numerical abnormalities of a number of chromosomes reported

• CESH profiling showed a uniform pattern of over- and underexpression of chromosome regions consistent with gene expression profiles established by DNA microarray analysis

• Uniform clinicopathological, DNA microarray and CESH profiles suggest that none of the described cytogenetic abnormalities play a primary pathogenetic role analysis,4 and which encode proteins of potential pathogenetic importance (Tables 29.2 and 29.3). However, neither cytogenetics nor gene-expression analysis have yet identified abnormalities common to all HCL cases that could explain the remarkable homogeneity of the disease, and at the same time provide clues concerning the events responsible for malignant transformation and maturational arrest of HCs.

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