Diagnosis and monitoring of chromosome aberrations in hematological malignancies by fluorescence in situ hybridization

Abstract

Besides its application in biological research, fluorescence in situ hybridization (FISH) is increasingly used for the cytogenetic analysis of human malignancies. Compared to conventional cytogenetic analysis, FISH allows delineation of specific numerical and structural chromosome aberrations in interphase cells (interphase cytogenetics). We have developed sets of genomic DNA probes for the identification of chromosome aberrations associated with chronic lymphocytic leukemia (CLL), chronic myeloid leukemias (CML), and acute myeloid leukemia (AML). In CLL, interphase cytogenetics will greatly contribute to the evaluation of the true incidence of specific chromosome aberrations and will provide the basis for more accurate correlations with the clinical outcome. The Philadelphia chromosome can be detected by FISH with high specificity and sensitivity in both CML and acute lymphoblastic leukemia. In CML, it can be used to better assess the cytogenetic remission status following therapy with interferon-alpha. Finally, in AML interphase cytogenetics provides a rapid and reliable technique for the identification of chromosome aberrations which are one of the most important prognostic factors in this disease. With the design of complex DNA probe sets and the development of digital microscopy and automated image analysis, it will be possible to use such disease-specific probe sets for monitoring residual disease following chemotherapy.

Minimal Residual Disease as a Predictive Factor for Relapse after Allogeneic Hematopoietic Stem Cell Transplant in Adult Patients with Acute Myeloid Leukemia in First and Second Complete Remission

“…Compared to conventional cytogenetic analysis, FISH allows for delineation of specific numerical and structural chromosome aberrations in interphase cells (interphase cytogenetics). FISH allows a quantification of cells carrying the aberration and the detection of chromosome abnormalities for which no PCR assays are available [12]. Very few studies of MRD in AML patients in morphologic remission undergoing allogeneic transplant have been reported, and the clinical significance of MRD detection by a variety of laboratory tools is still not clear.…”

Chromosomal abnormalities detected by multicolor fluorescence in situ hybridization in fine-needle aspirates from patients with small lymphocytic lymphoma are useful for predicting survival

“…CLL patients with 17p13 deletions have more advanced disease at diagnosis and a shorter median survival compared with those without the deletion. 4,5 In a study by Bryd et al, 17 CLL patients with 17p13 deletions detected by FISH had significantly lower response rates to rituximab therapy than those with other genetic abnormalities.…”

“…This multicolor FISH probe detects abnormalities of chromosomes 12, 11q22, 13q14.3, 13q34.3, and 17p13.1 and has been shown to be useful in predicting clinical outcome when used on blood and bone marrow samples from CLL patients. 4,5,[12][13][14][15][16][17] Chromosomal aberrations are reported in 60% to 80% of CLL/SLL cases with the use of FISH. 1 In SLL, the incidence of trisomy 12 ranges from 10% to 55% using FISH, 9 and its presence is associated with an atypical morphology.…”

“…[3][4][5][6] Chronic lymphocytic leukemia (CLL), which may include SLL as part of the disease spectrum, has chromosomal aberrations in 16% to 82% of cases, depending on the type of analysis. [6][7][8][9] Interphase fluorescence in situ hybridization (FISH) has an enhanced ability over conventional cytogenetics to detect specific chromosomal abnormalities 7,8 ; however, to our knowledge only a limited number of specific chromosomal abnormalities can be analyzed as a routine laboratory test.…”

“…Previous studies have analyzed primarily blood and bone marrow specimens in CLL/SLL patients 7,[10][11][12][13][14][15][16] and have been shown to be prognostically significant. 4,5,[12][13][14][15][16][17] In the current study, we evaluated this multicolor FISH probe on FNA specimens, comprised primarily of lymph nodes, from patients with a history of SLL/CLL and assessed the association between FISH findings and cytologic diagnoses, measures of cellular proliferation, and risk of death.…”