BACKGROUND AND OBJECTIVE: Patients with myelodysplastic syndromes (MDS) showing high numbers of abnormally localized immature precursors (ALIP) also display myelomonocytic antigens on immature cells, and it has been suggested that the presence of monocytosis could define a distinct subset of MDS characterized by poorer survival. The objective of this study was to analysis the incidence and significance of monocytosis among our series of patients with MDS and correlate the distributions of these elements with other hematologic features. METHODS: We evaluated the monocytic component in myelodysplastic syndromes in order to clarify the significance of monocytosis in MDS and its relationship with CMMoL and other MDS. Monocytosis was defined as a percentage of blood monocytes greater than 10%. RESULTS: Among a series of 139 consecutive MDS patients, we describe a group of 29 (20.8%) patients with monocytosis and dysplastic features involving multiple cell lineages which do not fulfill the criteria for diagnosis of CMMoL or aCML. These patients, who do not differ from MDS without monocytosis in the main clinical parameters, are characterized by relatively higher leukocyte (WBC 6.6 x 10(9)/L) and granulocyte counts (PMN 2.5 x 10(9)/L), hypercellular bone marrow and relatively poor prognosis. Among these patients, we observed a particularly high incidence of evolution to CMMoL (34.5%) and AML (17.2%) with monocytic component (FAB M4 and M5). Cytogenetic data demonstrated clonal chromosome changes in 11/13 patients with MDS and monocytosis, while only 19/41 patients without monocytosis showed clonal abnormalities. CONCLUSIONS AND PERSPECTIVES: The combination of hematologic and cytogenetic features in our study suggests that it is reasonable to consider myelodysplasia with monocytosis as a distinct disease subset of MDS, characterized by multilineage dysplasia along with a higher incidence of karyotype aberrations. The multi-step pathogenetic process in these patients may have reached a more advanced stage at which the relative or absolute increase in the number of monocytes may represent the first event in the subsequent progression of the disease towards acute leukemia.

Cell Lineage↗

PubMedDate not supplied

Detection of numerical aberrations in hematologic neoplasias by fluorescence in situ hybridization.

BACKGROUND AND OBJECTIVE: Over the last 5 years, fluorescence in situ hybridization (FISH) techniques have had an important impact on molecular cytogenetic diagnosis, providing a better understanding of the role of numerical aberrations in hemopoietic neoplasms. The objective of this article is to analyze the clinical applications of FISH in the management of hemopoietic malignancies. EVIDENCE AND INFORMATION SOURCES: The material examined in the present review includes articles and abstracts published in journals covered by the Science Citation Index and Medline, and personal published and unpublished data. STATE OF ART: FISH technology has the advantage of being relatively simple, fast and flexible. Published data and ongoing prospective studies show that, under well-controlled experimental conditions, interphase FISH is more sensitive than conventional metaphase analysis in the detection of numerical abnormalities. Due to the relatively high rate of false positive results, FISH cannot be used for the study of minimal residual disease. However, since molecular strategies for the detection of small-sized aneuploid clones have not been developed yet, FISH represents a useful adjunct to conventional cytogenetics, especially for the quantitation of the size of abnormal clones during the course of the disease and to monitor XX/XY chimerism following sex mis-matched bone marrow transplantation. Different approaches to the study of multiple cell-lineage involvement by chromosome changes have been developed that take advantage of FISH techniques by: a) simultaneous FISH and membrane immunophenotyping of cytologic and histologic preparations; b) two-step analysis based on assessment of the morphology of cells on panoptical stains, with subsequent hybridization and relocation of previously identified cells; c) FISH analysis of enriched cell fractions obtained by cell sorting or by separation of bone marrow cells on a density gradient, and d) study of single hemopoietic colonies grown in semisolid media. PERSPECTIVES: New molecular cytogenetic techniques, such as dual color FISH comparative genomic hybridization, are at hand that will greatly improve the diagnostic power of cytogenetics and make FISH increasingly useful in research laboratories as well as in clinical practice.

Aneuploidy↗