Skip to main content

Advertisement

SpringerLink
Log in

Juvenile myelomonocytic leukemia

  • Published:
Current Treatment Options in Oncology Aims and scope Submit manuscript

Opinion statement

Juvenile myelomonocytic leukemia is an aggressive neoplasia of early childhood. Only allogeneic stem cell transplantation (SCT) offers a long-term cure. In the absence of an HLA-matched family donor, early SCT from an unrelated donor will be the treatment of choice for most children. With clear evidence of a graft-versus-leukemia effect and a high post-transplant relapse rate, outcome of SCT will depend, in part, on the management of immunosuppression during the procedure. The impact of pretransplant cytoreductive treatment, such as intensive chemotherapy, splenectomy, or 13-cis retinoic acid, is unclear. Hypersensitivity for granulocyte-macrophage colony-stimulating factor and pathologic activation of the Ras/MAPK pathway play an important role in the pathophysiology of juvenile myelomonocytic leukemia and will provide the opportunity for several novel therapy approaches.

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 and Recommended Reading

  1. Niemeyer CM, Aricò M, Basso G, et al.: Chronic myelomonocytic leukemia in childhood: a report of 110 cases. Blood 1997, 89:3534–3543. This report is a comprehensive description of clinical features of the largest series of patients with JMML.

    PubMed  CAS  Google Scholar 

  2. Pinkel D: Differentiating juvenile myelomonocytic leukemia from infectious disease. Blood 1998, 91:365–367.

    PubMed  CAS  Google Scholar 

  3. Emanuel PD, Bates LJ, Castleberry RP, et al.: Selective hypersensitivity to granulocyte-macrophage colony-stimulating factor by juvenile chronic myeloid leukemia hematopoietic progenitors. Blood 1991, 77:925–929.

    PubMed  CAS  Google Scholar 

  4. Flotho C, Valcamonica S, Mach-Pascual S, et al.: RAS mutations and clonality analysis in children with juvenile myelomonocytic leukemia (JMML). Leukemia 1999, 13:32–37.

    Article  PubMed  CAS  Google Scholar 

  5. Side LE, Emanuel PD, Taylor B, et al.: Mutations of the NF1 gene in children with juvenile myelomonocytic leukemia without clinical evidence of neurofibromatosis, type 1. Blood 1998, 92:267–272.

    PubMed  CAS  Google Scholar 

  6. Side L, Taylor B, Cayouette M, et al.: Homozygous inactivation of the NF1 gene in bone marrow cells from children with neurofibromatosis type 1 and malignant myeloid disorders. N Engl J Med 1997, 336:1713–1720. This paper provides evidence that NF1 functions as a tumor suppressor gene in JMML and that neurofibromin is a regulator of Ras in early myelopoiesis.

    Article  PubMed  CAS  Google Scholar 

  7. Bollag G, Clapp DW, Shih S, et al.: Loss of NF1 results in activation of the RAS signaling pathway and leads to aberrant growth in haematopoietic cells. Nat Genet 1996, 12:144–148. This paper confirms the specific role of neurofibromin in negatively regulating GM-CSF signaling through Ras in hematopoietic cells.

    Article  PubMed  CAS  Google Scholar 

  8. Birnbaum RA, O’Marcaigh A, Wardak Z, et al.: NF1 and GM-CSF interact in myeloid leukemogenesis. Mol Cell 2000, 5:189–195.

    Article  PubMed  CAS  Google Scholar 

  9. Bader-Meunier B, Tchernia G, Mielot F, et al.: Occurrence of myeloproliferative disorder in patients with Noonan syndrome. J Pediatr 1997, 130:885–889.

    Article  PubMed  CAS  Google Scholar 

  10. Tartaglia M, Niemeyer CM, Song X, et al.: Somatic PTPN11 mutations in juvenile myelomonocytic leukemia, myelodysplastic syndromes and acute myeloid leukemia [abstract]. Blood 100:141a.

  11. Steinherz PG, Exelby PR, Young J, et al.: Splenectomy after angiographic embolization of the splenic artery in patients with massive splenomegaly and severe thrombocytopenia in juvenile subacute myelomonocytic leukemia. Med Pediatr Oncol 1984, 12:28–32.

    Article  PubMed  CAS  Google Scholar 

  12. Lutz P, Zix-Kieffer I, Souillet G, et al.: Juvenile myelomonocytic leukemia: analyses of treatment results in the EORTC Childrens Leukemia Cooperative Group (CLCG). Bone Marrow Transplant 1996, 18:1111–1116.

    PubMed  CAS  Google Scholar 

  13. Locatelli F, Niemeyer C, Angelucci E, et al.: Allogeneic bone marrow transplantation for chronic myelomonocytic leukemia in childhood: a report from the European Working Group on Myelodysplastic Syndrome in Childhood. J Clin Oncol 1997, 15:566–573. An analysis of many children transplanted for JMML. This paper is a good review and interpretation of published results of SCT in patients with JMML.

    PubMed  CAS  Google Scholar 

  14. Lilleyman JS, Harrison JF, Black JA: Treatment of juvenile chronic myeloid leukemia with sequential subcutaneous cytarabine and oral mercaptopurine. Blood 1977, 49:559–562.

    PubMed  CAS  Google Scholar 

  15. Castro-Malaspina H, Schaison G, Passe S, et al.: Subacute and chronic myelomonocytic leukemia in children (juvenile CML). Clinical and hematologic observations and identification of prognostic factors. Cancer 1984, 54:675–686.

    Article  PubMed  CAS  Google Scholar 

  16. Laver J, Kushner BH, Steinherz PG: Juvenile chronic myeloid leukemia: therapeutic insights. Leukemia 1987, 1:730–733.

    PubMed  CAS  Google Scholar 

  17. Chan HS, Estrov Z, Weitzman SS, et al.: The value of intensive combination chemotherapy for juvenile chronic myelogenous leukemia. J Clin Oncol 1987, 5:1960–1967.

    PubMed  CAS  Google Scholar 

  18. DeHeredia CD, Ortega JJ, Coll MT, et al.: Results of intensive chemotherapy in children with juvenile chronic myelomonocytic leukemia: a pilot study. Med Pediatr Oncol 1998, 31:516–520.

    Article  Google Scholar 

  19. Woods WG, Barnard DR, Alonzo TA, et al.: Prospective study of 90 children requiring treatment for juvenile myelomonocytic leukemia or myelodysplastic syndrome: a report from the Children’s Cancer Group. J Clin Oncol 2002, 20:434–440.

    Article  PubMed  Google Scholar 

  20. Festa RS, Shende A, Lanzkowsky P: Juvenile chronic myelocytic leukemia: experience with intensive combination chemotherapy. Med Pediatr Oncol 1990, 18:311–316.

    Article  PubMed  CAS  Google Scholar 

  21. Hasle H, Kerndrup G, Yssing M, et al.: Intensive chemotherapy in childhood myelodysplastic syndrome. A comparison with results in acute myeloid leukemia. Leukemia 1996, 10:1269–1273.

    PubMed  CAS  Google Scholar 

  22. Mirro J, Dow LW, Kalwinsky DK, et al.: Phase I-II study of continuous-infusion high-dose human lymphoblastoid interferon and the in vitro sensitivity of leukemic progenitors in nonlymphocytic leukemia. Cancer Treat Rep 1986, 70:363–367.

    PubMed  CAS  Google Scholar 

  23. Hazani A, Barak Y, Berant M, et al.: Congenital juvenile chronic myelogenous leukemia: therapeutical trial with interferon alpha-2. Med Pediatr Oncol 1993, 21:73–76.

    Article  PubMed  CAS  Google Scholar 

  24. Suttorp M, Rister M, Schmitz N: Interferon-alpha-2 (IFN) plus hydroxyurea for treatment of juvenile chronic myelogenous leukemia. Med Pediatr Oncol 1994, 22:358–359.

    Article  PubMed  CAS  Google Scholar 

  25. Aricò M, Nespoli L, Caselli D, et al.: Juvenile chronic myeloid leukaemia and alpha-interferon. Eur J Pediatr 1989, 148:379–380.

    Article  PubMed  Google Scholar 

  26. Maybee D, Dubowy R, Krischer J, et al.: Unusual toxicity of high-dose alpha interferon (aIFN) in the treatment of juvenile chronic myelogenous leukemia (JCML) [abstract]. Proc Am Soc Clin Oncol 1992, 1:950a.

    Google Scholar 

  27. Castleberry RP, Emanuel PD, Zuckerman KS, et al.: A pilot study of isotretinoin in the treatment of juvenile chronic myelogenous leukemia. N Engl J Med 1994, 331:1680–1684.

    Article  PubMed  CAS  Google Scholar 

  28. Pui CH, Arico M: Isotretinoin for juvenile chronic myelogenous leukemia. N Engl J Med 1995, 332:1520–1521.

    Article  PubMed  CAS  Google Scholar 

  29. Castleberry RP, Chang M, Maybee D, et al.: A phase II study of 13-cis retinoic acid in juvenile myelomonocytic leukemia [abstract]. Blood 1997, 90:346a.

    Google Scholar 

  30. Matthes-Martin S, Mann G, Peters C, et al.: Allogeneic bone marrow transplantation for juvenile myelomonocytic leukaemia: a single centre experience and review of the literature. Bone Marrow Transplant 2000, 26:377–382. A good review and interpretation of published results of SCT in patients with JMML.

    Article  PubMed  CAS  Google Scholar 

  31. Manabe A, Okamura J, Yumura-Yagi K, et al.: Allogeneic hematopoietic stem cell transplantation for 27 children with juvenile myelomonocytic leukemia diagnosed based on the criteria of the International JMML Working Group. Leukemia 2002, 16:645–649.

    Article  PubMed  CAS  Google Scholar 

  32. Sanders JE, Buckner CD, Thomas ED, et al.: Allogeneic marrow transplantation for children with juvenile chronic myelogenous leukemia. Blood 1988, 71:1144–1146.

    PubMed  CAS  Google Scholar 

  33. Smith FO, King R, Nelson G, et al.: Unrelated donor bone marrow transplantation for children with juvenile myelomonocytic leukaemia. Br J Haematol 2002, 116:716–724. This paper describes the result of unrelated donor transplants in a registered population.

    Article  PubMed  Google Scholar 

  34. Worth A, Rao K, Webb D, et al.: Successful treatment of juvenile myelomonocytic leukemia relapsing post stem cell transplant using donor lymphocyte infusion. Blood 2003, 101:1713–1714.

    Article  PubMed  CAS  Google Scholar 

  35. Iversen PO, Turczynowicz S, Lewis J, et al.: A second generation GM-CSF analogue that prevents dissemination and induces remission of human juvenile myelomonocytic leukemia in engrafted immunodeficient mice. Blood 1997, 90:4910–4917.

    PubMed  CAS  Google Scholar 

  36. Bernard F, Thomas C, Emile JF, et al.: Transient hematologic and clinical effect of E21R in a child with endstage juvenile myelomonocytic leukemia. Blood 2002, 99:2615–2616.

    Article  PubMed  CAS  Google Scholar 

  37. Frankel AE, Lilly M, Kreitman R, et al.: Diphtheria toxin fused to granulocyte-macrophage colony-stimulating factor is toxic to blasts from patients with juvenile myelomonocytic leukemia and chronic myelomonocytic leukemia. Blood 1998, 92:4279–4286.

    PubMed  CAS  Google Scholar 

  38. Emanuel PD, Snyder RC, Wiley T, et al.: Inhibition of juvenile myelomonocytic leukemia cell growth in vitro by farnesyltransferase inhibitors. Blood 2000, 95:639–645. This paper is an excellent summary of the pathophysiology of JMML.

    PubMed  CAS  Google Scholar 

  39. Mahgoub N, Taylor BR, Gratiot M, et al.: In vitro and in vivo effects of a farnesyltransferase inhibitor on NF1-deficient hematopoietic cells. Blood 1999, 94:2469–2476.

    PubMed  CAS  Google Scholar 

  40. Iversen PO, Emanuel PD, Sioud M: Targeting Raf-1 gene expression by a DNA enzyme inhibits juvenile myelomonocytic leukemia cell growth. Blood 2002, 99:4147–4153.

    Article  PubMed  CAS  Google Scholar 

  41. Iversen PO, Sorensen DR, Benestad HB: Inhibitors of angiogenesis selectively reduce the malignant cell load in rodent models of human myeloid leukemias. Leukemia 2002, 16:376–381.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Division of Pediatric Hematology and Oncology, Department of Pediatrics and Adolescent Medicine, University of Freiburg, Mathildenstrasse 1, 79106, Freiburg, Germany

    Charlotte Marie Niemeyer MD

Authors
  1. Charlotte Marie Niemeyer MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Christian Kratz MD
    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

Niemeyer, C.M., Kratz, C. Juvenile myelomonocytic leukemia. Curr. Treat. Options in Oncol. 4, 203–210 (2003). https://doi.org/10.1007/s11864-003-0021-z

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11864-003-0021-z

Keywords

Search

Navigation