Skip to Main Content

Cytogenetic analysis provides pathologists and clinicians with a powerful tool for the diagnosis and classification of hematologic malignant diseases. The detection of an acquired, somatic mutation establishes the diagnosis of a neoplastic disorder and rules out hyperplasia, dysplasia, or morphologic changes caused by toxic injury or vitamin deficiency. Specific cytogenetic abnormalities have been identified that are very closely, and sometimes uniquely, associated with morphologically distinct subsets of leukemia or lymphoma, enabling clinicians to predict their clinical course and likelihood of responding to particular treatments. The detection of one of these recurring abnormalities is helpful in establishing the diagnosis and adds information of prognostic importance. In many cases, the prognostic information derived from cytogenetic analysis is independent of that provided by other clinical features. Patients with favorable prognostic features benefit from standard therapies with well-known spectra of toxicities, whereas those with less favorable clinical and cytogenetic characteristics may be better treated with more intensive or investigational therapies. Pretreatment cytogenetic analysis also can be useful in choosing between postremission therapies that differ widely in cost, acute and chronic morbidity, and effectiveness. The appearance of new abnormalities in the karyotype of a patient under observation often signals clonal evolution and more aggressive behavior. The disappearance of a chromosomal abnormality present at diagnosis is an important indicator of complete remission following treatment, and its reappearance may herald disease recurrence.

Acronyms and Abbreviations

Acronyms and abbreviations that appear in this chapter include: ALCL, anaplastic large cell lymphoma; ALL, acute lymphocytic or lymphoblastic leukemia; AML, acute myelogenous leukemia; BL, Burkitt lymphoma; CDS, commonly deleted segment; CLL, chronic lymphocytic leukemia; CML, chronic myelogenous leukemia; DAPI, 4,6-diamidino-2-phenylindole-dihydrochloride; del, deletion; DLBCL, diffuse large B-cell lymphoma; EBV, Epstein-Barr virus; EFS, event-free survival; FAB, French-American-British; FISH, fluorescence in situ hybridization; IGH, immunoglobulin heavy chain; inv, inversion; ITD, internal tandem duplication; LOH, loss of heterozygosity; MDS, myelodysplastic syndrome; NHL, non-Hodgkin lymphoma; qRT-PCR, quantitative reverse transcriptase polymerase chain reaction; RA, refractory anemia; RAEB, refractory anemia with excess blasts; RARS, refractory anemia with ringed sideroblasts; RCMD, refractory cytopenia with multilineage dysplasia; SKY, spectral karyotyping; t, translocation; t-, therapy-related; WHO, World Health Organization.

Over the past two decades, the genes that are located at the breakpoints of a number of the recurring chromosomal translocations have been identified. Alterations in the expression of the genes or in the properties of the encoded proteins resulting from the rearrangement play an integral role in the process of malignant transformation.1,2 The altered genes fall into several functional classes, including tyrosine or serine protein kinases, cell surface receptors, growth factors, and the largest class, transcription factors. These latter proteins are involved in the induction or repression of gene transcription, often functioning in a tissue-specific fashion to regulate growth and differentiation.

There are two general mechanisms by which chromosomal translocations result in altered gene function. The first is deregulation of gene expression. This mechanism is characteristic of the translocations in lymphoid neoplasms ...

Pop-up div Successfully Displayed

This div only appears when the trigger link is hovered over. Otherwise it is hidden from view.