TY - JOUR
T1 - Fluorescent in situ hybridization (FISH) in bone marrow and peripheral blood of leukemia patients
T2 - Implications for occupational surveillance
AU - McDevitt, M. A.
AU - Condon, M.
AU - Stamberg, J.
AU - Karp, J. E.
AU - McDiarmid, M.
PY - 2007/4/20
Y1 - 2007/4/20
N2 - Although there has been a rapid rise in the application of fluorescent in situ hybridization (FISH) analysis of bone marrow tissue for the staging and prognosis determination of hematopoietic malignacies such as the chronic and acute leukemias, it's application as a surveillance tool for leukemogen exposed high risk occupational cohorts is understandably limited by the invasiveness of sample collection. While some small occupational studies have been performed using FISH in peripheral blood with promising results, some of the basic assumptions made in utilizing the FISH technique have not been fully explored. These include selection of the correct hematopoietic cell to assay (myeloid or lymphoid); selection of appropriate chromosomal markers and the sensitivity of peripheral blood FISH in detecting unbalanced genomic abnormalities. In this study, we performed a pilot 'validation' exercise utilizing the FISH technique and standard metaphase cytogenetics, comparing results in tandem pairs of peripheral blood with bone marrow cells, where clonal abnormalities arise. Samples were taken from patients with known chromosomal lesions associated with active leukemia. We carefully chose markers most frequently associated with leukemogen-inducing DNA damage and probes that have been utilized successfully in clinical practice. Ten de novo or therapy-related acute myeloid leukemia (t-AML) patients underwent bone marrow cell karyotyping and fluorescent in situ hybridization (FISH) analysis. Parallel peripheral blood samples were concommitently drawn and evaluated with FISH using the same probes. In six of eight paired samples treated with a 3-day phytohemagglutinin (PHA) stimulation, typically used to assay lymphocytes and their progenitors, we detected abnormal clones. In one of the two remaining cases, we identified an abnormal clone in both bone marrow and PHA-stimulated peripheral blood, although at a level in the peripheral blood sample that would typically be reported as "non-diagnostic" for clinical purposes. These results suggest that use of FISH in PHA stimulated peripheral blood samples with probes commonly employed in t-AML evaluations (chromosomes 5q, 7q, 8, 11q) to detect cytogenetic abnormalities in peripheral blood represents a potentially promising though as yet, under-utilized approach for the occupational surveillance of workers exposed to leukemogens, especially if it could be linked to automated high-throughput assays for increased sensitivity.
AB - Although there has been a rapid rise in the application of fluorescent in situ hybridization (FISH) analysis of bone marrow tissue for the staging and prognosis determination of hematopoietic malignacies such as the chronic and acute leukemias, it's application as a surveillance tool for leukemogen exposed high risk occupational cohorts is understandably limited by the invasiveness of sample collection. While some small occupational studies have been performed using FISH in peripheral blood with promising results, some of the basic assumptions made in utilizing the FISH technique have not been fully explored. These include selection of the correct hematopoietic cell to assay (myeloid or lymphoid); selection of appropriate chromosomal markers and the sensitivity of peripheral blood FISH in detecting unbalanced genomic abnormalities. In this study, we performed a pilot 'validation' exercise utilizing the FISH technique and standard metaphase cytogenetics, comparing results in tandem pairs of peripheral blood with bone marrow cells, where clonal abnormalities arise. Samples were taken from patients with known chromosomal lesions associated with active leukemia. We carefully chose markers most frequently associated with leukemogen-inducing DNA damage and probes that have been utilized successfully in clinical practice. Ten de novo or therapy-related acute myeloid leukemia (t-AML) patients underwent bone marrow cell karyotyping and fluorescent in situ hybridization (FISH) analysis. Parallel peripheral blood samples were concommitently drawn and evaluated with FISH using the same probes. In six of eight paired samples treated with a 3-day phytohemagglutinin (PHA) stimulation, typically used to assay lymphocytes and their progenitors, we detected abnormal clones. In one of the two remaining cases, we identified an abnormal clone in both bone marrow and PHA-stimulated peripheral blood, although at a level in the peripheral blood sample that would typically be reported as "non-diagnostic" for clinical purposes. These results suggest that use of FISH in PHA stimulated peripheral blood samples with probes commonly employed in t-AML evaluations (chromosomes 5q, 7q, 8, 11q) to detect cytogenetic abnormalities in peripheral blood represents a potentially promising though as yet, under-utilized approach for the occupational surveillance of workers exposed to leukemogens, especially if it could be linked to automated high-throughput assays for increased sensitivity.
KW - Chromosomes 5 and 7
KW - FISH
KW - Occupational leukemogen exposure
KW - Secondary hematological malignancy
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UR - http://www.scopus.com/inward/citedby.url?scp=33947574470&partnerID=8YFLogxK
U2 - 10.1016/j.mrgentox.2007.01.002
DO - 10.1016/j.mrgentox.2007.01.002
M3 - Article
C2 - 17276720
AN - SCOPUS:33947574470
VL - 629
SP - 24
EP - 31
JO - Mutation Research - Genetic Toxicology and Environmental Mutagenesis
JF - Mutation Research - Genetic Toxicology and Environmental Mutagenesis
SN - 1383-5718
IS - 1
ER -