Overview

In the last 30 years, information provided by cytogenetic analysis has become indispensable for the clinical management of patients with hematological malignancies. Metaphase chromosome analysis of bone marrow (BM) cells enables the entire genome to be screened for evidence of chromosomal changes, which provide the landmarks for the genes involved in leukemogenesis. Up to 80% of patients with acute lymphoblastic leukemia (ALL) and 70% of patients with acute myeloid leukemia (AML) have abnormal karyotypes. A large number of these chromosomal changes are recurrent and have been associated with specific morphological types in both myeloid and lymphoid lineages.[1] As a result, the finding of an abnormal cytogenetic clone may provide the definitive diagnosis. Besides, some chromosomal abnormalities are independent prognostic indicators. Certain karyotypes are associated with a good prognosis, whereas others indicate a poor outcome, leading to the administration of alternative therapies. One illustrative example is AML. In this leukemia, the favorable prognostic subgroup is defined by the presence of leukemic blasts with t(15;17), t(8;21), or inv(16). Unfavorable cases are those with abnormalities involving more than two chromosomes, monosomy 5/5q- or 7/7q-, or rearrangements of the long arm of chromosome 3. The survival rate of patients from this group is less than 20% at 5 years.[2] These patients represent a considerable therapeutic challenge for which no current treatment approach is satisfactory. The patients with a normal karyotype or cytogenetic abnormalities that are not included in these other categories are characterized as having an intermediate risk of relapse.

Conventional cytogenetic analysis is based on the study of metaphase chromosomes by banding techniques. Because it needs tumor metaphases to be analyzed, viable tumor cells have to be obtained from fresh material and cultured. Although highly precise, this technique requires skilled personnel and is time consuming and expensive. These factors have led investigators to seek alternative methods for identifying chromosomal abnormalities. The technique of fluorescence in situ hybridization (FISH) is one such method. At present, FISH is used largely to detect known chromosomal abnormalities using specific DNA probes. The high sensitivity and specificity of FISH, the speed with which the method can be accomplished (virtually overnight), and the ability to provide information from nondividing cells (interphase FISH) have made this molecular cytogenetic technique a powerful tool for genetic analysis.[3] The ability to examine nondividing cells or slowly cycling cells is particularly important in the analysis of some lymphoid neoplasias, in which cytoge-netic analysis is often hampered by the small number or absence of mitotic cells. For instance, in chronic lymphocytic leukemia (CLL), G-banding analysis is informative in only a minority of cases, whereas FISH

can detect chromosomal abnormalities in up to 80% of cases.[4] In a short time FISH, such as the G-banding analysis, has become a screening test to identify recurring chromosomal abnormalities associated with hematologic malignant diseases.

Getting Started With Dumbbells

Getting Started With Dumbbells

The use of dumbbells gives you a much more comprehensive strengthening effect because the workout engages your stabilizer muscles, in addition to the muscle you may be pin-pointing. Without all of the belts and artificial stabilizers of a machine, you also engage your core muscles, which are your body's natural stabilizers.

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