[1302] Clinical Utility of Fluorescence In Situ Hybridization for Detection of Del(5q) in Myelodysplasia and Acute Myeloid Leukemia

Y Sun, JR Cook. Cleveland Clinic, OH

Background: Fluorescence in situ hybridization (FISH) studies for del(5q) may assist in the diagnosis and classification of myelodysplastic syndromes (MDS), and may also help guide the choice of therapy, given the efficacy of lenalidomide in cases containing this abnormality. It is currently unclear which chromosomal loci are the most appropriate to examine for detection of del(5q) in routine practice, and it is unclear in which situations FISH studies may increase the diagnostic yield over metaphase cytogenetics (MC) alone. Two commonly deleted regions have been described on chromosome 5q: one occurs in acute myeloid leukemia (AML) and high grade MDS and includes EGR1 at 5q31, while the second, occurring in at least some cases reported as 5q- syndrome, is centered around CSF1R at 5q33. We first examined whether FISH for EGR1, CSF1R or both provides the greatest sensitivity for detection of del(5q). Next, we examined the additional diagnostic yield of FISH studies over MC alone.
Design: First, FISH for EGR1 and CSF1R (Abbott Molecular, Abbott Park, IL) were performed on 51 archived bone marrows (AML, n=21; MDS, n=30) containing del(5q) by MC. Next, results of FISH for EGR1 (performed at a reference laboratory or at the Cleveland Clinic) were compared to results of MC in 183 bone marrow samples obtained for known or suspected MDS or AML.
Results: Of 51 cases containing del(5q) by MC, FISH studies were positive for EGR1 deletion in 49 (96%), including each of 8 cases of 5q- syndrome. CSF1R deletion was identified in 44/48 cases (92%), each of which also showed deletion of EGR1. 2 cases (4%) were positive for EGR1 deletion but normal for CSF1R, while 2 cases showed del(5q) by MC only. In 183 cases of known or suspected MDS/AML, MC showed an abnormal karyotype in 57 (31%) including del(5q) in 15 cases (8%). FISH studies were positive for EGR1 deletion in 18 cases overall, including each case with del(5q) by MC and 3 cases that showed no growth or fewer than 20 normal metaphases by MC.
Conclusions: FISH for EGR1 deletion detects del(5q) in the vast majority of cases of MDS or AML containing this abnormality, including at least most cases of 5q- syndrome. Additional studies for CSF1R deletion rarely increase the diagnostic yield. In routine practice, MC alone provides reliable detection of del(5q) in most cases, and a small percentage of cases are detectable only by MC. However, FISH studies assist in the identification of del(5q) when suboptimal numbers of metaphases are obtained for MC.
Category: Hematopathology

Wednesday, March 11, 2009 1:00 PM

Poster Session VI # 192, Wednesday Afternoon