Highly sensitive fluorescence in situ hybridization method to detect double BCR/ABL fusion and monitor response to therapy in chronic myeloid leukemia

Gordon W. Dewald, William A. Wyatt, Amy L. Juneau, Richard O. Carlson, Alan R. Zinsmeister, Syed M. Jalal, Jack L. Spurbeck, Richard T. Silver

Research output: Contribution to journalArticle

158 Citations (Scopus)

Abstract

We investigated a new method using fluorescence in situ hybridization and DNA probes that span the common break-points of t(9;22)(q34;q11.2) and that detect double BCR/ABL fusion (D-FISH) in bone marrow cells with this translocation, one on the abnormal chromosome 9 and one on the Philadelphia chromosome (Ph chromosome). D-FISH patterns were abnormal in 30 of 30 specimens with classic, simple, complex, and masked Ph chromosomes. Based on 200 nuclei from each of 30 normal specimens, the mean percentage of false- positive cells was 0.25 ± 0.39. Thirty-seven specimens from 10 patients were studied before treatment and two or more times at 4-month intervals after treatment with interferon-α(2b) (IFN-α(2b)) with or without ara-C. Based on 200 nuclei, the results of D-FISH in these specimens correlated closely with quantitative cytogenetics and accurately quantified disease within a few percent. We studied 6,000 nuclei for each of six specimens, three normal and three from patients with chronic myeloid leukemia (CML) in cytogenetic remission. The normal cutoff for 6,000 nuclei was 0.079% and patients in cytogenetic remission had residual disease ranging from 7 (0.117%)to 53 (0.883%) Ph-positive nuclei. We conclude that D-FISH can detect the ph chromosome and its variant translocations and accurately quantify disease in CML at diagnosis and at all times after treatment, including cytogenetic remission.

Original languageEnglish (US)
Pages (from-to)3357-3365
Number of pages9
JournalBlood
Volume91
Issue number9
StatePublished - May 1 1998
Externally publishedYes

Fingerprint

Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Chromosomes
Fluorescence In Situ Hybridization
Cytogenetics
Fusion reactions
Fluorescence
Cells
Philadelphia Chromosome
Chromosomes, Human, Pair 9
Cytarabine
DNA Probes
Therapeutics
Bone Marrow Cells
Interferons
Bone

ASJC Scopus subject areas

  • Hematology

Cite this

Dewald, G. W., Wyatt, W. A., Juneau, A. L., Carlson, R. O., Zinsmeister, A. R., Jalal, S. M., ... Silver, R. T. (1998). Highly sensitive fluorescence in situ hybridization method to detect double BCR/ABL fusion and monitor response to therapy in chronic myeloid leukemia. Blood, 91(9), 3357-3365.

Highly sensitive fluorescence in situ hybridization method to detect double BCR/ABL fusion and monitor response to therapy in chronic myeloid leukemia. / Dewald, Gordon W.; Wyatt, William A.; Juneau, Amy L.; Carlson, Richard O.; Zinsmeister, Alan R.; Jalal, Syed M.; Spurbeck, Jack L.; Silver, Richard T.

In: Blood, Vol. 91, No. 9, 01.05.1998, p. 3357-3365.

Research output: Contribution to journalArticle

Dewald, GW, Wyatt, WA, Juneau, AL, Carlson, RO, Zinsmeister, AR, Jalal, SM, Spurbeck, JL & Silver, RT 1998, 'Highly sensitive fluorescence in situ hybridization method to detect double BCR/ABL fusion and monitor response to therapy in chronic myeloid leukemia', Blood, vol. 91, no. 9, pp. 3357-3365.
Dewald GW, Wyatt WA, Juneau AL, Carlson RO, Zinsmeister AR, Jalal SM et al. Highly sensitive fluorescence in situ hybridization method to detect double BCR/ABL fusion and monitor response to therapy in chronic myeloid leukemia. Blood. 1998 May 1;91(9):3357-3365.
Dewald, Gordon W. ; Wyatt, William A. ; Juneau, Amy L. ; Carlson, Richard O. ; Zinsmeister, Alan R. ; Jalal, Syed M. ; Spurbeck, Jack L. ; Silver, Richard T. / Highly sensitive fluorescence in situ hybridization method to detect double BCR/ABL fusion and monitor response to therapy in chronic myeloid leukemia. In: Blood. 1998 ; Vol. 91, No. 9. pp. 3357-3365.
@article{6f5f2c92df4643eea62d88f2479f2472,
title = "Highly sensitive fluorescence in situ hybridization method to detect double BCR/ABL fusion and monitor response to therapy in chronic myeloid leukemia",
abstract = "We investigated a new method using fluorescence in situ hybridization and DNA probes that span the common break-points of t(9;22)(q34;q11.2) and that detect double BCR/ABL fusion (D-FISH) in bone marrow cells with this translocation, one on the abnormal chromosome 9 and one on the Philadelphia chromosome (Ph chromosome). D-FISH patterns were abnormal in 30 of 30 specimens with classic, simple, complex, and masked Ph chromosomes. Based on 200 nuclei from each of 30 normal specimens, the mean percentage of false- positive cells was 0.25 ± 0.39. Thirty-seven specimens from 10 patients were studied before treatment and two or more times at 4-month intervals after treatment with interferon-α(2b) (IFN-α(2b)) with or without ara-C. Based on 200 nuclei, the results of D-FISH in these specimens correlated closely with quantitative cytogenetics and accurately quantified disease within a few percent. We studied 6,000 nuclei for each of six specimens, three normal and three from patients with chronic myeloid leukemia (CML) in cytogenetic remission. The normal cutoff for 6,000 nuclei was 0.079{\%} and patients in cytogenetic remission had residual disease ranging from 7 (0.117{\%})to 53 (0.883{\%}) Ph-positive nuclei. We conclude that D-FISH can detect the ph chromosome and its variant translocations and accurately quantify disease in CML at diagnosis and at all times after treatment, including cytogenetic remission.",
author = "Dewald, {Gordon W.} and Wyatt, {William A.} and Juneau, {Amy L.} and Carlson, {Richard O.} and Zinsmeister, {Alan R.} and Jalal, {Syed M.} and Spurbeck, {Jack L.} and Silver, {Richard T.}",
year = "1998",
month = "5",
day = "1",
language = "English (US)",
volume = "91",
pages = "3357--3365",
journal = "Blood",
issn = "0006-4971",
publisher = "American Society of Hematology",
number = "9",

}

TY - JOUR

T1 - Highly sensitive fluorescence in situ hybridization method to detect double BCR/ABL fusion and monitor response to therapy in chronic myeloid leukemia

AU - Dewald, Gordon W.

AU - Wyatt, William A.

AU - Juneau, Amy L.

AU - Carlson, Richard O.

AU - Zinsmeister, Alan R.

AU - Jalal, Syed M.

AU - Spurbeck, Jack L.

AU - Silver, Richard T.

PY - 1998/5/1

Y1 - 1998/5/1

N2 - We investigated a new method using fluorescence in situ hybridization and DNA probes that span the common break-points of t(9;22)(q34;q11.2) and that detect double BCR/ABL fusion (D-FISH) in bone marrow cells with this translocation, one on the abnormal chromosome 9 and one on the Philadelphia chromosome (Ph chromosome). D-FISH patterns were abnormal in 30 of 30 specimens with classic, simple, complex, and masked Ph chromosomes. Based on 200 nuclei from each of 30 normal specimens, the mean percentage of false- positive cells was 0.25 ± 0.39. Thirty-seven specimens from 10 patients were studied before treatment and two or more times at 4-month intervals after treatment with interferon-α(2b) (IFN-α(2b)) with or without ara-C. Based on 200 nuclei, the results of D-FISH in these specimens correlated closely with quantitative cytogenetics and accurately quantified disease within a few percent. We studied 6,000 nuclei for each of six specimens, three normal and three from patients with chronic myeloid leukemia (CML) in cytogenetic remission. The normal cutoff for 6,000 nuclei was 0.079% and patients in cytogenetic remission had residual disease ranging from 7 (0.117%)to 53 (0.883%) Ph-positive nuclei. We conclude that D-FISH can detect the ph chromosome and its variant translocations and accurately quantify disease in CML at diagnosis and at all times after treatment, including cytogenetic remission.

AB - We investigated a new method using fluorescence in situ hybridization and DNA probes that span the common break-points of t(9;22)(q34;q11.2) and that detect double BCR/ABL fusion (D-FISH) in bone marrow cells with this translocation, one on the abnormal chromosome 9 and one on the Philadelphia chromosome (Ph chromosome). D-FISH patterns were abnormal in 30 of 30 specimens with classic, simple, complex, and masked Ph chromosomes. Based on 200 nuclei from each of 30 normal specimens, the mean percentage of false- positive cells was 0.25 ± 0.39. Thirty-seven specimens from 10 patients were studied before treatment and two or more times at 4-month intervals after treatment with interferon-α(2b) (IFN-α(2b)) with or without ara-C. Based on 200 nuclei, the results of D-FISH in these specimens correlated closely with quantitative cytogenetics and accurately quantified disease within a few percent. We studied 6,000 nuclei for each of six specimens, three normal and three from patients with chronic myeloid leukemia (CML) in cytogenetic remission. The normal cutoff for 6,000 nuclei was 0.079% and patients in cytogenetic remission had residual disease ranging from 7 (0.117%)to 53 (0.883%) Ph-positive nuclei. We conclude that D-FISH can detect the ph chromosome and its variant translocations and accurately quantify disease in CML at diagnosis and at all times after treatment, including cytogenetic remission.

UR - http://www.scopus.com/inward/record.url?scp=0032079490&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0032079490&partnerID=8YFLogxK

M3 - Article

C2 - 9558393

AN - SCOPUS:0032079490

VL - 91

SP - 3357

EP - 3365

JO - Blood

JF - Blood

SN - 0006-4971

IS - 9

ER -