Y. Manor

Trisomies 9 and 8 detected by fluorescence in situ hybridization in patients with systemic mastocytosis

BACKGROUND Systemic mastocytosis is a rare disease characterized by proliferation of mast cells in one or more organs. The origin of the mast cells is still debated, although it has been recently shown that they derive from CD34+ hematopoietic progenitors. Some clinical and in vitro studies have suggested a possible link between myeloproliferative disorders and systemic mast cell disease. OBJECTIVE This study was designed to further evaluate the association between systemic mast cell disease and other hematologic disorders by means of conventional cytogenetic analysis and fluorescent in situ hybridization. METHODS We used cytogenetic analysis and fluorescent in situ hybridization with probes to chromosomes 8 and 9 in six patients with systemic mast cell disease. RESULTS Fluorescent in situ hybridization helped to identify five patients with trisomy 9 and one with trisomy 8. In contrast, chromosomal analysis demonstrated an abnormal karyotype (45,XO/46,XY) in only one patient. CONCLUSION The association between myeloproliferation disorders and systemic mast cell disease may be explained by the finding that trisomy 9 and trisomy 8 are common in both disorders. A trisomy was detected in all of the patients in our small group compared with nearly 40% of previously reported patients with myeloproliferative disorders. FISH is more sensitive than conventional cytogenetics in detecting these aberrations.

Fluorescence in situ hybridization for the detection of trisomies 8 and 9 in polycythemia vera.

Trisomies 8 and 9 are the most common numerical chromosome abnormalities in polycythemia vera (PCV). Their role in the pathogenesis of the disease is unclear, however, as is their diagnostic or prognostic value. We evaluated fluorescent in situ hybridization as compared to chromosome analysis for the detection of trisomies 8 or 9 in peripheral blood cells of PCV patients. We demonstrated that FISH is a more sensitive method for the detection of the abnormalities. A positive correlation between the duration of the disease and trisomy 9 was found. FISH is a sensitive, convenient, and rapid method for the diagnosis and follow-up of chromosome aberrations in patients with PCV. The application of FISH to a larger cohort of patients may provide valuable information regarding the role of the chromosomal aberrations in the initiation and progression of this disease.

Clinical detection of BCR-ABL fusion by in situ hybridization in chronic myelogenous leukemia

We describe the use of the fluorescence in situ hybridization (FISH) technique to detect residual Philadelphia chromosome-positive (Ph+) cells in a patient with blastic phase chronic myelogenous leukemia (CML) after aggressive cytoreductive treatment. The analysis was made in interphase nuclei because of the very small number of recognizable metaphases in leukemic patients. FISH was a reliable tool for the detection of chromosome translocations in interphase nuclei as compared with conventional cytogenetic and polymerase chain reaction (PCR) techniques.

Replication Pattern in Cancer: Asynchronous Replication in Multiple Myeloma and in Monoclonal Gammopathy

In this study we evaluated the replication pattern and cell-cycle dynamics of cells from patients considered to have a premalignant condition (monoclonal gammopathy, or MGUS) and patients with multiple myeloma (MM), as well as healthy controls. We applied the fluorescence in situ hybridization (FISH) technique with the TP53, RB-1 and 21q22 loci on the patients cells. Asynchrony was determined by the presence of one single and one set of double dots in the same cell. The rate of asynchronic replication was significantly higher in the cells from MM patients, with intermediate value in the cells from MGUS, while the lowest rate was in cells from controls. We suggest that these results may reflect the changes in gene replication and cell-cycle progression that occur in premalignant and malignant cells.

The detection of trisomies 8 and 9 in patients with essential thrombocytosis by fluorescence in situ hybridization

Essential thrombocytosis (ET) is a clonal, chronic myeloproliferative disorder (MPD) originating from a multipotent stem cell. To date no specific cytogenetic marker has been found in ET. It was recently reported that chromosomal aberrations have been detected by fluorescence in situ hybridization (FISH) in patients with normal karyotypes or nonanalyzable metaphases. Therefore, we evaluated whether trisomies 8 and 9, which are commonly found in MPDs, can be detected in ET by FISH and compared the results with chromosome analysis. Peripheral blood mononuclear cells of patients with essential thrombocytosis were studied by classical chromosome banding and by FISH. We used biotin labeled alpha satellite of chromosome 8 and biotin labeled beta satellite of chromosome 9 as probes for the FISH studies. FISH detected 5 patients with trisomy 8 and 5 with trisomy 9 of the 18 patients evaluated. No trisomy was found by cytogenetic studies. The trisomies were detected by FISH in only a minority of the cells. No correlation was found between the presence of a trisomy and clinical characteristics. FISH is a sensitive method for the detection of trisomies 8 and 9 in patients with ET. The common finding of these chromosomal aberrations in MPD suggests that genes associated with myeloid proliferation are located on these chromosomes. Standardization of interphase cytogenetics is needed before this technique can be accepted for routine use in the clinic.

Kaposi's sarcoma and angioimmunoblastic lymphadenopathy

Kaposis sarcoma (KS) and angioimmunoblastic lymphadenopathy (AILD) are exceptionally rare neoplastic diseases, although the former has recently been more frequently reported among certain populations, and is lately a topic for extensive medical and investigational interest. This case is unique in that it describes an association between KS and AILD. Such an association raises the question of a common pathogenic mechanism. The authors believe that predisposition to each of both diseases may be related to acquired immune deffiency which in turn may be induced by specific viral infections.

Fluorescence in situ hybridization (FISH) for retrospective detection of trisomies 3 and 7 in multiple myeloma

The malignant plasma cells of multiple myeloma (MM) have a low proliferative activity and therefore cytogenetic studies of the disease have been severely limited. We evaluated the role of fluorescence in situ hybridization (FISH) in the detection of numerical chromosomal abnormalities in early stages of myeloma and the applicability of the method to stored archival slides. Old air-dried bone marrow smears from 15 myeloma patients obtained at presentation were probed with alpha satellite DNA sequences to chromosomes 3 and 7. Numerical chromosome aberrations were found in eight (53%) of the patients, including six (of 12) with trisomy 7, and two (of eight) with trisomy 3. This study demonstrates that FISH is a sensitive method for the detection of numerical aberrations in myeloma and for the study of old slides for retrospective analysis.

Acute Anuric Bilateral Ureteral Obstruction in Malignant Lymphoma

Two cases of bilateral ureteral obstruction in malignant lymphoma are reported. In one case, primary infiltration of the ureters by Hodgkins disease was demonstrated, while in the other the obstruction was due to ureteral compression by enlarged lymph nodes. The diagnostic procedures and the management of such cases are discussed.

Detection of bcl rearrangements in B-CLL by fluorescence in situ hybridization

Data concerning oncogene activation in CLL are very limited. When studied by Southern blot, rearrangements of bcl-1, bcl-2, and bcl-3 have been only infrequently reported. We evaluated the role of fluorescence in situ hybridization (FISH) in the detection of gene rearrangements in two CLL patients. We used multiple DNA probes, including those of chromosome 12, immunoglobulin heavy and light chains, and the oncogenes bcl-1, bcl-2, and bcl-3. Additionally, routine cytogenetic study was performed. In one patient, trisomy 12 and bcl-2 translocation were demonstrated by both methods, while trisomy 12 and bcl-1 translocation were seen in the second patient, who had a normal karyotype. Larger studies should evaluate the role of FISH in the detection of oncogene involvement in CLL and compare it with other molecular methods.