Comparison between conventional banding analysis and FISH screening with an AML-specific set of probes in 260 patients

Abstract

Fluorescence in situ hybridization (FISH) is becoming popular in the diagnosis of clonal chromosomal abnormalities. We set up a fast FISH procedure using an extensive set of specific probes. Conventional banding analysis (CBA) and FISH were compared in 260 newly diagnosed acute myeloid leukemia (AML) patients. For FISH the following probes were used: MLL, CBF-beta/MYH11, ETV-6/AML1; AML1/ETO, BCR/ABL, PML/RAR, c-MYC, TP53, RB1, 5q31/5p15.2, 5q33-34, 7q31/CEP7, 20q13; CEP 4, X, Y. Result time was 96 h for CBA versus 5 h for FISH from direct harvest. CBA showed clonal abnormalities in 41% (n=105/260), normal karyotype in 39% (n=102/260) and failed in 20% (n=53/260). FISH screened all patients and detected abnormalities in 39% (n=102/260); CBA and FISH together identified abnormalities in 49% (n=128/260). In six patients with normal CBA and in eight patients with clonal karyotype, it detected further cryptic abnormalities. CBA showed clonal abnormalities in 13% of patients negative at FISH (n=21/158). FISH screening does not add relevant information to CBA, but is the quickest method for detecting major genetic abnormalities in AML. The speed of FISH is very valuable in AML-M3/M3v because PML/RAR+ patients require specific therapy. Furthermore, we suggest FISH screening in failed, complex or suboptimal quality chromosome and specific FISH analysis for 5q, 7q, 12p, 17p, inv(16), t(11q23) in order to implement CBA accuracy.

Potential clinical impact of three-dimensional visualization for fluorescent in situ hybridization image analysis

“…1 For example, aiming to improve accuracy of leukemia diagnosis, a number of prospective clinical trials were conducted in the last several years to assess the clinical utility of FISH technology. [2][3][4][5][6] These studies confirmed that FISH supplemented standard the karyotyping method by detecting abnormalities in interphase nuclei and clarifying cryptic or complex abnormalities. As a result, the current USA National Cancer Institute guidelines recommended the incorporation of interphase FISH test to the diagnostic workup of leukemia patients, in particular for all patients diagnosed and confirmed with chronic myeloid leukemia (CLL).…”

High-resolution genome-wide array-based comparative genome hybridization reveals cryptic chromosome changes in AML and MDS cases with trisomy 8 as the sole cytogenetic aberration

“…Cytogenetically visible hemizygous deletions involving this region are common in leukemias, 1 but deletions have also been described in a handful of AMLs with cytogenetically normal chromosomes 12, including one case with þ 8 in addition to a del(11)(q13). 27,28 The pathogenetic importance of these deletions in AML is unknown, as is the target gene. As previously reported deletions have not all encompassed ETV6, it has been suggested that loss of CDKN1B may instead be the biologically important outcome.…”

Acute Myeloid Leukemia with the t(8;21) Translocation: Clinical Consequences and Biological Implications

“…Tandem analysis with RT-PCR and flow cytometry can improve MRD detection [205]. Interphase FISH may also have a potential as an adjunct analysis to cytomorphology, cytogenetics, or multiparameter flow cytometry in the identification of MRD, since strong agreement between these methods has been described in large cohorts [206–208]. …”