del(17p) in myeloid malignancies

1999-12-01   Claude Preudhomme , Jean-Luc Lai , Marc Zandecki , Pierre Fenaux , Vaérie Soenen-Cornu 

1.Laboratoire d Hématologie A Hôpital Albert, Calmette - CHRU de Lille, Boulevard du Pr Leclercq 59037, Lille Cedex, France

Clinics and Pathology

Disease

acute non lymphocytic leuemia/myelodysplastic syndromes (AML/MDS), chronic myelogenous leukemia (CML) in blast crisis

Phenotype stem cell origin

mainly refractory anemia with excess of blasts RAEB/ RAEB-t in MDS, often M2 or M6 in AML / multi-lineage involvement

Etiology

about 30% of AML and MDS with 17p deletion are therapy related; t-AML and t-MDS occur after a lymphoïd neoplasm or a solid tumor treated by chemotherapy with an alkylating agent or after essential thrombocytemia or polycythemia vera treated by hydroxyurea alone or associated with other drugs

Epidemiology

  • 3 to 4% of AML and MDS
  • mean age > 60 years
  • sex ratio : about 1M/1F
  • Clinics

    not specific (consequences of cytopenias infection, bleeding, anemia)
    Atlas Image

    Cytology

  • most cases of AML and MDS with 17p deletion have a particular form of morphological dysgranulopoiesis, combining both nuclear and cytoplasmic abnormalities in at least 5% of neutrophils; affected cells have reduced size and are mostly mature; nucleus is bi- or non-lobulated and chromatin is well- or heavily-clumped; cytoplasm contains variable number of small clear vacuoles and sometimes a reduced number of granules; these morphological abnormalities involve neutrophilic, but also eosinophilic and basophilic lineages; such abnormalities can be observed both in the bone marrow and in the peripheral blood; however, in the latter instance, it may be difficult to demonstrate pseudo-Pelger Huüt anomaly, due to frequent neutropenia; these nuclear changes mimick those found in the so-called constitutional Pelger-Huüt hypolobulation of polymorphonuclear leukocytes
  • dysgranulopoiesis features are frequently associated with variable degree of dyserythropoiesis and dysmegakaryocytopoiesis
  • Pathology

    not reported
    Atlas Image
    17p syndrome - Text and iconography Courtesy Georges Flandrin 2005.

    Treatment

    classical anthracycline-Ara C chemotherapy gives poor results; the only possibility of cure appears to be by allogeneic stem cell transplantation, but very few allografted cases have been reported

    Evolution

    worsening of cytopenias, progression to AML

    Prognosis

    very poor, median survival: 4 months

    Cytogenetics

    Cytogenetics morphological

    17p deletions result mainly from unbalanced translocation between 17p and another chromosome and less frequently from monosomy 17, isochromosome 17q and partial 17p deletion; chromosome 5 is the partner chromosome the most frequently involved in the unbalanced translocation, other involved chromosomes are mainly chromosomes 7, 12, 18, 21 and 22

    Cytogenetics molecular

    the breakpoint on chromosome 17 and the extent of the deletion of 17p are variable, but the breakpoint is always proximal to the p53 gene; the variable extent of 17p deletion suggests the presence of tumor suppressor gene(s) on 17p, inactivated by the deletion. The p53 gene is a good candidate

    Additional anomalies

    chromosome 17p rearrangement or monosomy 17 are frequently associated to at least 2 other chromosomal rearrangements and are therefore part of complex abnormalities; the most frequent additional abnormalities include chromosomes 5 and/or 7, but also chromosomes 12, 16 and 11; complex karyotypes are associated in some cases with unidentified ring or marker chromosomes; however, some cases of iso(17q) are isolated or associated with a few additional chromosome anomalies

    Genes Involved and Proteins

    Gene name
    TP53 (Tumour protein p53 (Li-Fraumeni syndrome))
    Location
    17p13.1

    Result of the Chromosomal Anomaly

    Description

    inactivation of the P53 gene by deletion of one allele and mutation of the non deleted allele

    Detection protocole

  • p53 deletion : conventional cytogenetics, FISH with p53 specific probes
  • p53 mutation : SSCP or immunocytochemistry
  • Bibliography

    Pubmed IDLast YearTitleAuthors
    19125531991P53 gene mutations in acute myeloid leukemia with 17p monosomy.Fenaux P et al
    15507731992Mutations of the P53 gene in acute myeloid leukaemia.Fenaux P et al
    91306241997The 17p-syndrome: a distinct myelodysplastic syndrome entity?Jary L et al
    17666711991Mutations in the p53 gene in myelodysplastic syndromes.Jonveaux P et al
    34606271986Diagnostic significance of detecting pseudo-Pelger-Huët anomalies and micro-megakaryocytes in myelodysplastic syndrome.Kuriyama K et al
    23404881990Translocations (5;17) and (7;17) in patients with de novo or therapy-related myelodysplastic syndromes or acute nonlymphocytic leukemia. A possible association with acquired pseudo-Pelger-Huët anomaly and small vacuolated granulocytes.Laï JL et al
    78850351995Myelodysplastic syndromes and acute myeloid leukemia with 17p deletion. An entity characterized by specific dysgranulopoïesis and a high incidence of P53 mutations.Lai JL et al
    80576711994Detection of p53 mutations in hematological malignancies: comparison between immunocytochemistry and DNA analysis.Lepelley P et al
    100258991999Therapy-related myelodysplastic syndrome and acute myeloid leukemia with 17p deletion. A report on 25 cases.Merlat A et al
    93323021997The clinical significance of mutations of the P53 tumour suppressor gene in haematological malignancies.Preudhomme C et al
    34701171987Correlation between acquired pseudo-Pelger-Huet anomaly and involvement of chromosome 17 in chronic myeloid leukemia.Sessarego M et al
    95197881998Myelodysplasia during the course of myeloma. Restriction of 17p deletion and p53 overexpression to myeloid cells.Soenen V et al
    94277171998Acute myeloid leukemia and myelodysplastic syndromes following essential thrombocythemia treated with hydroxyurea: high proportion of cases with 17p deletion.Sterkers Y et al
    79491871994p53 mutations are associated with resistance to chemotherapy and short survival in hematologic malignancies.Wattel E et al

    Summary

    Note

    recently, we and others reported in AML and MDS a strong correlation between 17p deletion (a clonal cytogenetic anomaly consisting of a deletion of the short arm of chromosome 17), and a particular form of morphological dysgranulopoiesis, we also found in such cases a strong correlation between 17p deletion and p53 mutation; these correlations suggest that AML and MDS with 17p deletion constitute a new morphological-cytogenetic-molecular entity, the " 17p syndrome "
    Atlas Image
    17p syndrome R- banding: various rearrangements of chromosomes 5 and/or 7, and 17 - Courtesy Jean-Luc Lai

    Citation

    Claude Preudhomme ; Jean-Luc Lai ; Marc Zandecki ; Pierre Fenaux ; Vaérie Soenen-Cornu

    del(17p) in myeloid malignancies

    Atlas Genet Cytogenet Oncol Haematol. 1999-12-01

    Online version: http://atlasgeneticsoncology.org/haematological/1142/del(17p)-in-myeloid-malignancies

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