International Journal of Hematology

, Volume 80, Issue 2, pp 155–158 | Cite as

Fluorescent In Situ Hybridization Analysis of Philadelphia Chromosome-Negative Chronic Myeloid Leukemia with the bcr/abl Fusion Gene

  • Fumihiko Monma
  • Kazuhiro Nishii
  • Shunji Yamamori
  • Noboru Hosokai
  • Takahiro Nakazaki
  • Felipe Lorenzo V
  • Eiji Usui
  • Miho Sakakura
  • Hiroyuki Miyashita
  • Atsushi Fujieda
  • Kohshi Ohishi
  • Naoyuki Katayama
  • Hiroshi Shiku
Case Report

Abstract

This report describes a patient with Philadelphia chromosome-negative (Ph-) but bcr/abl fusion gene-positive chronic myeloid leukemia (CML) and a molecular analysis of the mechanisms behind the Ph- status. Spectral karyotyping-fluorescent in situ hybridization (SKY-FISH) analysis showed no abnormal translocation; however, a bcr/abl fusion gene was detected by reverse transcriptase-polymerase chain reaction analysis. FISH analysis showed that signals from the 9q and 22q subtelomere probes were detected on the der(9) and der(22) chromosomes, respectively. On the other hand, FISH analysis of the abl and bcr genes with dual fusion probes, which can detect the bcr/abl fusion gene on both the der(9) and der(22) chromosomes, showed the signal for bcr/abl fusion on the der(22) chromosome but not on the der(9) chromosome.These results indicate that insertion of the abl gene into the bcr region on the der(22) chromosome or retranslocation between the der(9) chromosome and the der(22) chromosome may have caused the Ph- CML in this case.

Key words

Philadelphia chromosome Masked Ph t(9) t(22) CML Imatinib Fish Ph-negative CML 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Cortes JE, Talpaz M, Beran M, et al. Philadelphia chromosomenegative chronic myelogenous leukemia with rearrangement of the breakpoint cluster region: long term follow-up results. Cancer. 1995;75:464–470.CrossRefPubMedGoogle Scholar
  2. 2.
    Takahashi N, Miura I, Ohshima A, et al. Duplication of chromosome 9 carrying a BCR/ABL chimeric gene in Philadelphia chromosome negative chronic myeloid leukemia. Cancer Genet Cytogenet. 1996;89:166–169.CrossRefPubMedGoogle Scholar
  3. 3.
    Kurzrock R, Blick MD, Talpaz M, et al. Rearrangement in the breakpoint cluster region and the clinical course in Philadelphianegative chronic myelogenous leukemia. Ann Intern Med. 1986;105:673–679.CrossRefPubMedGoogle Scholar
  4. 4.
    van der Plas DC, Hermans ABC, Soekarman D, et al. Cytogenetic and molecular analysis in Philadelphia negative CML. Blood. 1989;73:1038–1044.PubMedGoogle Scholar
  5. 5.
    Goldman JM, Melo JV. Chronic myeloid leukemia: advances in biology and new approaches to treatment. N Engl J Med. 2003;349:1451–1464.CrossRefPubMedGoogle Scholar
  6. 6.
    Weinstein ME, Grossman A, Perle MA, et al. The karyotype of Philadelphia chromosome-negative, bcr rearrangement-positive chronic myeloid leukemia. Cancer Genet Cytogenet. 1988;35:223–229.CrossRefPubMedGoogle Scholar
  7. 7.
    Calabrese G, Stuppia M, Franchi PG, et al. Complex translocation of the Ph chromosome and Ph negative CML arise from similar mechanisms, as evidenced by FISH analysis. Cancer Genet Cytogenet. 1994;78:153–159.CrossRefPubMedGoogle Scholar
  8. 8.
    Hagemeijer A, Buijs A, Smit E, et al. Translocation of BCR to chromosome 9: a new cytogenetic variant detected by FISH in two Phnegative, BCR-positive patients with chronic myeloid leukemia. Genes Chromosomes Cancer. 1993;8:237–245.CrossRefPubMedGoogle Scholar
  9. 9.
    Inazawa J, Nishigaki H, Takahira H, et al. Rejoining between 9q+ and Philadelphia chromosomes results in normal-looking chromosomes 9 and 22 in Ph1-negative chronic myelocytic leukemia. Hum Genet. 1989;83:115–118.CrossRefPubMedGoogle Scholar
  10. 10.
    Morris CM, Heisterkamp N, Kennedy MA, Fitzgerald PH, Groffen J. Ph-negative chronic myeloid leukemia: molecular analysis of ABL insertion into M-BCR on chromosome 22. Blood. 1990;76:1812–1818.PubMedGoogle Scholar
  11. 11.
    Tanaka K, Minamihisamatu M, Yagi S, et al. Two step mechanism for formation of complex 9;22 chromosome translocation in chronic myelocytic leukemia detected by fluorescence in situ hybridization. Exp Oncol. 2001;23:29–38.Google Scholar
  12. 12.
    Sokal JE, Cox EB, Baccarani M, et al. Prognostic discrimination in “good-risk” chronic granulocytic leukemia. Blood. 1984;63:789–799.PubMedGoogle Scholar
  13. 13.
    Hasford J, Pfirrmann M, Hehlmann R, et al. A new prognostic score for survival of patients with chronic myeloid leukemia treated with interferon alfa: Writing Committee for the Collaborative CML Prognostic Factors Project Group. J Natl Cancer Inst. 1998;90:850–858.CrossRefPubMedGoogle Scholar
  14. 14.
    Kantarjian HM, Keating MJ, Smith TL, Talpaz M, McCredie KB. Proposal for simple synthesis prognostic staging system in chronic myelogenous leukemia. Am J Med. 1990;88:1–8.CrossRefPubMedGoogle Scholar
  15. 15.
    Nishii K, Usui E, Sakakura M, et al. Additional t(11;17)(q23;q21) in a patient with Philadelphia-positive mixed lineage antigenexpressing leukemia. Cancer Genet Cytogenet. 2001;126:8–12.CrossRefPubMedGoogle Scholar
  16. 16.
    Talpaz M, Kantarjian HM, Kurzrock R, Trujillo JM, Gutterman JU. Interferon-alpha produces sustained cytogenetic responses in chronic myelogenous leukemia: Philadelphia chromosome-positive patients. Ann Intern Med. 1991;114:532–538.CrossRefPubMedGoogle Scholar
  17. 17.
    El-Zimaity MMT, Kantarjian HM, Talpaz M, et al. Results of imatinib mesylate therapy in chronic myelogenous leukemia with variant Philadelphia chromosome. Br J Haematol. 2004;125:187–195.CrossRefPubMedGoogle Scholar
  18. 18.
    Nishii K, Usui E, Katayama N, et al. Characteristics of t(8;21) acute myeloid leukemia (AML) with additional chromosomal abnormality: concomitant trisomy 4 may constitute a distinctive subtype of t(8;21) AML. Leukemia. 2003;17:731–737.CrossRefPubMedGoogle Scholar
  19. 19.
    Osumi K, Fukui T, Kiyoi H, et al. Rapid screening of leukemia fusion transcripts in acute leukemia by real-time PCR. Leuk Lymphoma. 2002;43:2291–2299.CrossRefPubMedGoogle Scholar

Copyright information

© The Japanese Society of Hematology 2004

Authors and Affiliations

  • Fumihiko Monma
    • 1
  • Kazuhiro Nishii
    • 1
  • Shunji Yamamori
    • 2
  • Noboru Hosokai
    • 2
  • Takahiro Nakazaki
    • 3
  • Felipe Lorenzo V
    • 1
  • Eiji Usui
    • 1
  • Miho Sakakura
    • 1
  • Hiroyuki Miyashita
    • 1
  • Atsushi Fujieda
    • 1
  • Kohshi Ohishi
    • 1
  • Naoyuki Katayama
    • 1
  • Hiroshi Shiku
    • 1
  1. 1.Second Department of Internal MedicineMie University School of MedicineMieJapan
  2. 2.Mitsubishi Kagaku Bio-Clinical Laboratories, IncTokyo
  3. 3.Internal MedicineTakeuchi HospitalMieJapan

Personalised recommendations