Skip to main content

Advertisement

SpringerLink
Log in

Further evidence for the molecular heterogeneity of chronic myeloid leukemia

  • Original Article
  • Published:
Annals of Hematology Aims and scope Submit manuscript

Summary

Cytogenetic and molecular techniques were performed on samples obtained from 29 patients with chronic myelocytic leukemia (CML); 27 were in the chronic phase and two were in blast crisis. A further five cases were also analyzed, two with atypical CML (aCML), one with chronic neutrophilic leukemia (CNL), and two with juvenile CML (JCML). Most of the cases with typical CML were Philadelphia chromosome (Ph) positive and had a rearrangement within the major breakpoint cluster region (M-bcr). One of these cases was shown to be Ph positive but showed no rearrangement within the M-bcr. Two cases with clinical features typical of CML were Ph negative. One of these showed a rearrangement within the M-bcr, but no rearrangement was demonstrated in the other. Both patients in blast crisis were Ph positive and M-bcr positive. One showed a second Ph. Patients with aCML were Ph negative and had no M-bcr rearrangement. A polymorphism within the M-bcr was found withBglII in one case. No Ph chromosome or M-bcr rearrangement was found in CNL or JCML. These data support the molecular heterogeneity reported in CML.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Bartam CR, Carbonel F (1986) bcr Rearrangement in Ph-negative CML. Cancer Genet Cytogenet 21: 183–184

    Google Scholar 

  2. Bartram CR, Kleihaver E, deKlein A, Grosveld G, Teyssier JR, Heisterkamp N, Groffen J (1985) c-abl and bcr rearranged in a Ph-negative CML patient. EMBO J 4: 683–686

    Google Scholar 

  3. Birnie GD, Mills KI, Benn P (1989) Does the site of the breakpoint on chromosome 22 influence the duration of the chronic phase in chronic myeloid leukemia? Leukemia 3: 545–547

    Google Scholar 

  4. Blennerhassett GT, Furth ME, Anderson A, Burns JP, Chaganti RSK, Blick M, Talpaz M, Dev VG, Chan LC, Wiedemann LM, Greaves MF, Hagemeijer A, van der Plas D, Skuse G, Wang N, Stam K (1988) Clinical evaluation of a DNA probe assay for the Philadelphia (Ph) translocation in chronic myelogenous leukemia. Leukemia 2: 648–657

    Google Scholar 

  5. Butturini A, Gale RP (1990) Oncogenes and leukemia. Leukemia 4: 138–160

    Google Scholar 

  6. De Braekeleer M (1986) Breakpoint distribution in variant Philadelphia translocations in chronic myeloid leukemia. Nouv Rev Fr Hematol 28: 293–295

    Google Scholar 

  7. Donato CD, Croci G, Lazzari S, Scarduelli L, Vignoli R, Buia M, Tramaloni C, Maccari S, Plancher AC (1986) Chronic neutrophilic leukemia: description of a new case with karyotypic abnormalities. Am J Clin Pathol 85: 369–371

    Google Scholar 

  8. Eisenberg A, Silver R, Soper L, Arlin Z, Coleman M, Bernhardt B, Benn P (1988) The location of breakpoints within the breakpoint cluster region (bcr) of chromosome 22 in chronic myeloid leukemia. Leukemia 2: 642–647

    Google Scholar 

  9. Ezdinli EZ, Sokal JE, Crosswhite L, Sandberg AA (1970) Philadelphia chromosome-positive and-negative chronic myelocytic leukemia. Ann Intern Med 72: 175–182

    Google Scholar 

  10. Fitzgerald PH, Beard MEJ, Morris CM, Heaton DC, Reeve AE (1987) Ph-negative chronic myeloid leukemia. Br J Haematol 66: 311–314

    Google Scholar 

  11. Freedman MH, Estrov Z, Chan HSL (1988) Juvenile chronic myelogenous leukemia. Am J Pediatr Hematol Oncol 10: 261–267

    Google Scholar 

  12. Gale RP (1987) Chronic myelogenous leukaemia: a model for human cancers. Clin Haematol 1: 869–886

    Google Scholar 

  13. Gale RP, Goldman JM (1988) Rapid progress in chronic myelogenous leukemia. Leukemia 2: 321–324

    Google Scholar 

  14. Ganesan TS, Rassool F, Guo AP, Thing KH, Dowding C, Hibbin JA, Young BD, White H, Kumaran TO, Galton DAG, Goldman JM (1986) Rearrangement of the bcr gene in Philadelphia chromosome-negative chronic myeloid leukemia. Blood 68: 957–960

    Google Scholar 

  15. Groffen J, Stephenson JR, Heisterkamp N, deKlein A, Bartram CR, Grosveld G (1984) Philadelphia chromosomal breakpoint are cluster within a limited region, bcr, on chromosome 22. Cell 36: 93–99

    Google Scholar 

  16. Grossman A, Mathew A, O'Connell MP, Tiso P, Distenfeld A, Benn P (1990) Multiple restriction enzyme digests are required to rule out polymorphism in the molecular diagnosis of chronic myeloid leukemia. Leukemia 4: 63–64

    Google Scholar 

  17. Kantarjian HM, Keating MJ, Walters RS, McCredie KB, Smith TL, Talpaz M, Beran M, Cork A, Trujillo JM, Freireich E (1986) Clinical and prognostic features of Philadelphia chromosome-negative chronic myelogenous leukemia. Cancer 58: 2023–2030

    Google Scholar 

  18. Kurzrock R, Kantarjian HM, Shtalrid M, Gutterman JU, Talpaz M (1990) Philadelphia chromosome-negative chronic myelogenous leukemia without breakpoint cluster region rearrangement: a chronic myeloid leukemia with a distinct clinical course. Blood 75: 445–452

    Google Scholar 

  19. Kurzrock R, Gutterman JU, Talpaz M (1988) The molecular genetics of Philadelphia chromosome-positive leukemias. N Engl J Med 319: 990–998

    Google Scholar 

  20. Lee MS, LeMaistre A, Kantarjian HM, Talpaz M, Freireich EJ, Trujillo JM, Stass SA (1989) Detection of two alternative bcr/abl mRNA junctions and minimal residual disease in Philadelphia chromosome-positive chronic myelogenous leukemia by polymerase chain reaction. Blood 73: 2165–2170

    Google Scholar 

  21. Maniatis T, Fritsch EF, Sambrook J (1982) Molecular cloning: a laboratory manual. Cold Spring Harbor, New York

    Google Scholar 

  22. Mertens F, Johansson B, Heim S, Kristoffersson U, Mandahl N, Turesson I, Malm O, Othzen A, Bartram CR, Catovsky D, Mitelman F (1990) Trisomy 14 in atypical chronic myeloid leukemia. Leukemia 4: 117–120

    Google Scholar 

  23. Nowell PC, Hungerford DA (1960) A minute chromosome in human chronic granulocytic leukemia. Science 132: 1497–1499

    Google Scholar 

  24. Ogawa H, Sugiyama H, Soma T, Masaoka T, Kishimoto S (1989) No correlation between location of bcr breakpoints and clinical states in Ph-positive CML patients. Leukemia 3: 492–496

    Google Scholar 

  25. Saglio G, Guerrasio A, Tassinari A, Ponzetto C, Zaccaria A, Testoni P, Celso B, Cambrin GR, Serra A, Pegoraro L, Avanzi CG, Attadia V, Falda M, Gavosto F (1988) Variability of the molecular defects corresponding to the presence of a Philadelphia chromosome in human hematologic malignancies. Blood 72: 1203–1208

    Google Scholar 

  26. Seabright M (1983) A rapid banding technique for human chromosomes. Lancet 2: 971

    Google Scholar 

  27. Selleri L, Narni F, Emilia G, Colo A, Zucchini P, Venturelli D, Donelli A, Torelli U, Torelli G (1987) Philadelphia-positive chronic myeloid leukemia with a chromosome 22 breakpoint outside the breakpoint cluster region. Blood 70: 1659–1664

    Google Scholar 

  28. Shepherd PCA, Ganesan TS, Galton DAG (1987) Haematological classification of the chronic myeloid leukaemias. Clin Haematol 1: 887–906

    Google Scholar 

  29. Southern EM (1975) Detection of specific sequence among DNA fragments separated by gel electrophoresis. J Mol Biol 98: 507–517

    Google Scholar 

  30. Torelli G, Selleri L, Emilia G, Narni F, Colo A, Zucchini P, Donelli A, Venturelli D, Torelli U (1987) Molecular study of the Philadelphia translocation in chronic myelogenous leukemia in different stages of disease. Haematologica 72: 201–208

    Google Scholar 

  31. van der Feltz MJM, Shivji MKK, Grosveld G, Wiedemann LM (1988) Characterization of the translocation breakpoint in a patient with Philadelphia-positive, bcr-positive acute lymphoblastic leukaemia. Oncogene 3: 215–219

    Google Scholar 

  32. Wiedemann LM, Karhi KK, Shivji MKK, Rayter SI, Pegram SM, Doeden G, Bevan D, Will A, Galton DAG, Chan LC (1988) The correlation of breakpoint cluster region rearrangement and 210 phl/abl expression with morphological analysis of Phnegative chronic myeloid leukemia and other myeloproliferative diseases. Blood 71: 349–355

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Departments of Molecular Biology and Clinical Hematology, Instituto de Hematologia e Inmunologia, La Habana, Cuba

    A. Hernandez, L. Corral, A. Muñiz, C. Alaez, E. Espinosa, G. Martinez & P. Hernandez

Authors
  1. A. Hernandez
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. L. Corral
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. A. Muñiz
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. C. Alaez
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. E. Espinosa
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. G. Martinez
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. P. Hernandez
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Hernandez, A., Corral, L., Muñiz, A. et al. Further evidence for the molecular heterogeneity of chronic myeloid leukemia. Ann Hematol 62, 217–220 (1991). https://doi.org/10.1007/BF01729835

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF01729835

Key words

Search

Navigation