Atypical Chronic Myeloid Leukemia (aCML)

2008-06-01   Jesus M Hernandez  , Teresa Villaescusa  , Maryam Arefi  , Lucía López  , Juan L Garcia  

1.Unidad de Citogenetica Oncologica, Servicio de Hematologia, Hospital Universitario de Salamanca, Paseo San Vicente 58-182, 37007 Salamanca, Spain

Clinics and Pathology

Disease

aCML is a chronic myeloproliferative disorder with a clinical and hematological picture similar to chronic myelogenous leukemia (CML) but lacking Philadelphia chromosome and BCR - ABL or PDGFRBeta rearangements. Atypical CML is characterized by the combination of: 10-20% of immature granulocytes; marked granulocytic dysplasia and both less than 2% of basophils and less than 10% of monocytes.

Phenotype stem cell origin

Presumably a multipotential stem cell.

Epidemiology

ACML is a rare disorder of old adults. No predominance of sex. The incidence is not established.

Clinics

Anemic syndrome. Splenomegaly. Malaise.

Cytology

  • Peripheral blood: Leukocytosis with a high count of immature granulocytes. By definition monocytes are less than 10% and basophils less than 2%. Anemia is more frequent than thrombocytopenia.
  • Bone marow: Hypercellular with myelodysplastic features of the three series, most marked in granulocytic lineage. Blast cell infiltration ranges from 0% to 10%.

    • Treatment

    Hydroxyurea is indicated, although not curative, in old patients. Complete remission may be achieved after chemotherapy based on anthracyclin and citarabine (an acute myeloblastic leukemia therapy schedule). Allogeneic bone marrow transplantation is the only curative therapy for those patients who are eligible. Some cases may achieve a complete hematological response after interferon therapy.

    Prognosis

    The median survival is about 24 months with standart therapy. Some cases have a progression to acute myeloblastic leukemia.

    Genes Involved and Proteins

    Note
    The mechanisms of oncogenesis in aCML remains to be elucidated. In the last years some cases displaying rearrangement PDGFRb have been reported. Most of these cases showed PDGFRb / ETV6 fusion, but also a fusion with H4 gene (located at 10q22), have been described. A total of 8 different genes have been found fused to PDGFRb gene. The diagnosis of these cytogenetic abnormalities are critical since most these cases could achieve a complete cytogenetic response with imatinib therapy. The JAK2V617F activating tyrosine kinase mutation is unfrequent in aCML.

    Article Bibliography

    Pubmed IDLast YearTitleAuthors
    125424822003Novel translocations that disrupt the platelet-derived growth factor receptor beta (PDGFRB) gene in BCR-ABL-negative chronic myeloproliferative disorders.Baxter EJ et al
    79867171994The chronic myeloid leukaemias: guidelines for distinguishing chronic granulocytic, atypical chronic myeloid, and chronic myelomonocytic leukaemia. Proposals by the French-American-British Cooperative Leukaemia Group.Bennett JM et al
    169601512007Durable responses to imatinib in patients with PDGFRB fusion gene-positive and BCR-ABL-negative chronic myeloproliferative disorders.David M et al
    145040722003Imatinib mesylate elicits positive clinical response in atypical chronic myeloid leukemia involving the platelet-derived growth factor receptor beta.Garcia JL et al
    105778571999World Health Organization classification of neoplastic diseases of the hematopoietic and lymphoid tissues: report of the Clinical Advisory Committee meeting-Airlie House, Virginia, November 1997.Harris NL et al
    108474632000Clinical, hematological and cytogenetic characteristics of atypical chronic myeloid leukemia.Hernández JM et al
    113873652001BCR rearrangement-negative chronic myelogenous leukemia revisited.Kurzrock R et al
    86160211996Atypical chronic myeloid leukaemia, a distinct clinical entity related to the myelodysplastic syndrome?Oscier DG et al
    113890342001H4(D10S170), a gene frequently rearranged in papillary thyroid carcinoma, is fused to the platelet-derived growth factor receptor beta gene in atypical chronic myeloid leukemia with t(5;10)(q33;q22).Schwaller J et al
    158606612005The JAK2 V617F activating tyrosine kinase mutation is an infrequent event in both "atypical" myeloproliferative disorders and myelodysplastic syndromes.Steensma DP et al
    178822802008Classification and diagnosis of myeloproliferative neoplasms: the 2008 World Health Organization criteria and point-of-care diagnostic algorithms.Tefferi A et al

    Summary

    Note

    The nosology of aCML is controversial. The FAB classification includes aCML in the group of chronic myeloid leukemias. The WHO classification has classified aCML in the group of myelodysplastic/myeloproliferative diseases.

    Citation

    Jesus M Hernandez ; Teresa Villaescusa ; Maryam Arefi ; Lucía López ; Juan L Garcia

    Atypical Chronic Myeloid Leukemia (aCML)

    Atlas Genet Cytogenet Oncol Haematol. 2008-06-01

    Online version: http://atlasgeneticsoncology.org/haematological/2117/js/lib/gene-explorer/favicon/favicon-16x16.png

    Historical Card

    2001-09-01 Atypical Chronic Myeloid Leukemia (aCML) by  Norma C Gutierrez,Jesus M Hernandez 

    Unidad de Citogenetica Oncologica, Servicio de Hematologia, Hospital Universitario de Salamanca, Paseo San Vicente 58-182, 37007 Salamanca, Spain