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del(17p) in myeloid malignancies

Identity

Note recently, we and others reported in ANLL 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 ANLL and MDS with 17p deletion constitute a new morphological-cytogenetic-molecular entity, the " 17p syndrome "
Other names17p syndrome in myeloid malignancies
 
  17p syndrome R- banding: various rearrangements of chromosomes 5 and/or 7, and 17 - Courtesy Jean-Luc Lai

Clinics and Pathology

Disease acute non lymphocytic leuemia/myelodysplastic syndromes (ANLL/MDS), chronic myelogenous leukemia (CML) in blast crisis
Phenotype / cell stem origin mainly refractory anemia with excess of blasts RAEB/ RAEB-t in MDS, often M2 or M6 in ANLL / multi-lineage involvement
Etiology about 30% of ANLL and MDS with 17p deletion are therapy related; t-ANLL 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 ANLL and MDS
  • mean age > 60 years
  • sex ratio : about 1M/1F
  • Clinics not specific (consequences of cytopenias infection, bleeding, anemia)
    Cytology
  • most cases of ANLL 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 Huët anomaly, due to frequent neutropenia; these nuclear changes mimick those found in the so-called constitutional Pelger-Huët hypolobulation of polymorphonuclear leukocytes
  • dysgranulopoiesis features are frequently associated with variable degree of dyserythropoiesis and dysmegakaryocytopoiesis
  • Pathology not reported
     
    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 ANLL
    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 P53
    Location 17p13.1

    Result of the chromosomal anomaly

    Hybrid gene
    Description inactivation of the P53 gene by deletion of one allele and mutation of the non deleted allele
    Detection
  • p53 deletion : conventional cytogenetics, FISH with p53 specific probes
  • p53 mutation : SSCP or immunocytochemistry
  •   

    To be noted

    in few 17p deletion cases, whole chromosomal painting and fluorescence in situ hybridization (FISH) analysis with p53 specific probe demonstrate that unidentified ring or marker chromosomes observed in conventional cytogenetic can contain 17p material including the second p53 allele; in these few cases, the particular form of morphological dysgranulopoiesis abnormalities observed in ³ 17p- syndrome ² are not observed

    Translocations implicated (Data extracted from papers in the Atlas)

     del(17p) in myeloid malignancies

    External links

    Mitelman database
    del(17p) - Mitelman database (CGAP - NCBI)

    Bibliography

    Diagnostic significance of detecting pseudo-Pelger-Huˆ´t anomalies and micro-megakaryocytes in myelodysplastic syndrome.
    Kuriyama K, Tomonaga M, Matsuo T, Ginnai I, Ichimaru M
    British journal of haematology. 1986 ; 63 (4) : 665-669.
    PMID 3460627
     
    Correlation between acquired pseudo-Pelger-Huet anomaly and involvement of chromosome 17 in chronic myeloid leukemia.
    Sessarego M, Ajmar F
    Cancer genetics and cytogenetics. 1987 ; 25 (2) : 265-270.
    PMID 3470117
     
    Translocations (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-Huˆ´t anomaly and small vacuolated granulocytes.
    LaˆØ JL, Zandecki M, Fenaux P, Le Baron F, Bauters F, Cosson A, Deminatti M
    Cancer genetics and cytogenetics. 1990 ; 46 (2) : 173-183.
    PMID 2340488
     
    P53 gene mutations in acute myeloid leukemia with 17p monosomy.
    Fenaux P, Jonveaux P, Quiquandon I, LaˆØ JL, Pignon JM, Loucheux-Lefebvre MH, Bauters F, Berger R, Kerckaert JP
    Blood. 1991 ; 78 (7) : 1652-1657.
    PMID 1912553
     
    Mutations in the p53 gene in myelodysplastic syndromes.
    Jonveaux P, Fenaux P, Quiquandon I, Pignon JM, LaˆØ JL, Loucheux-Lefebvre MH, Goossens M, Bauters F, Berger R
    Oncogene. 1991 ; 6 (12) : 2243-2247.
    PMID 1766671
     
    Mutations of the P53 gene in acute myeloid leukaemia.
    Fenaux P, Preudhomme C, Quiquandon I, Jonveaux P, LaˆØ JL, Vanrumbeke M, Loucheux-Lefebvre MH, Bauters F, Berger R, Kerckaert JP
    British journal of haematology. 1992 ; 80 (2) : 178-183.
    PMID 1550773
     
    Detection of p53 mutations in hematological malignancies: comparison between immunocytochemistry and DNA analysis.
    Lepelley P, Preudhomme C, Vanrumbeke M, Quesnel B, Cosson A, Fenaux P
    Leukemia : official journal of the Leukemia Society of America, Leukemia Research Fund, U.K. 1994 ; 8 (8) : 1342-1349.
    PMID 8057671
     
    Detection of p53 mutations in hematological malignancies: comparison between immunocytochemistry and DNA analysis.
    Lepelley P, Preudhomme C, Vanrumbeke M, Quesnel B, Cosson A, Fenaux P
    Leukemia : official journal of the Leukemia Society of America, Leukemia Research Fund, U.K. 1994 ; 8 (8) : 1342-1349.
    PMID 8057671
     
    p53 mutations are associated with resistance to chemotherapy and short survival in hematologic malignancies.
    Wattel E, Preudhomme C, Hecquet B, Vanrumbeke M, Quesnel B, Dervite I, Morel P, Fenaux P
    Blood. 1994 ; 84 (9) : 3148-3157.
    PMID 7949187
     
    Myelodysplastic syndromes and acute myeloid leukemia with 17p deletion. An entity characterized by specific dysgranulopoˆØesis and a high incidence of P53 mutations.
    Lai JL, Preudhomme C, Zandecki M, Flactif M, Vanrumbeke M, Lepelley P, Wattel E, Fenaux P
    Leukemia : official journal of the Leukemia Society of America, Leukemia Research Fund, U.K. 1995 ; 9 (3) : 370-381.
    PMID 7885035
     
    The 17p-syndrome: a distinct myelodysplastic syndrome entity?
    Jary L, Mossafa H, Fourcade C, Genet P, Pulik M, Flandrin G
    Leukemia & lymphoma. 1997 ; 25 (1-2) : 163-168.
    PMID 9130624
     
    The clinical significance of mutations of the P53 tumour suppressor gene in haematological malignancies.
    Preudhomme C, Fenaux P
    British journal of haematology. 1997 ; 98 (3) : 502-511.
    PMID 9332302
     
    17p Deletion in acute myeloid leukemia and myelodysplastic syndrome. Analysis of breakpoints and deleted segments by fluorescence in situ.
    Soenen V, Preudhomme C, Roumier C, Daudignon A, LaˆØ JL, Fenaux P
    Blood. 1998 ; 91 (3) : 1008-1015.
    PMID 9446663
     
    Myelodysplasia during the course of myeloma. Restriction of 17p deletion and p53 overexpression to myeloid cells.
    Soenen V, Preudhomme C, Roumier C, LaˆØ JL, Lepelley P, Facon T, Pagniez D, Fenaux P
    Leukemia : official journal of the Leukemia Society of America, Leukemia Research Fund, U.K. 1998 ; 12 (2) : 238-241.
    PMID 9519788
     
    Acute myeloid leukemia and myelodysplastic syndromes following essential thrombocythemia treated with hydroxyurea: high proportion of cases with 17p deletion.
    Sterkers Y, Preudhomme C, LaˆØ JL, Demory JL, Caulier MT, Wattel E, Bordessoule D, Bauters F, Fenaux P
    Blood. 1998 ; 91 (2) : 616-622.
    PMID 9427717
     
    Therapy-related myelodysplastic syndrome and acute myeloid leukemia with 17p deletion. A report on 25 cases.
    Merlat A, Lai JL, Sterkers Y, Demory JL, Bauters F, Preudhomme C, Fenaux P
    Leukemia : official journal of the Leukemia Society of America, Leukemia Research Fund, U.K. 1999 ; 13 (2) : 250-257.
    PMID 10025899
     
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    Last year articlesautomatic search in PubMed

    Contributor(s)

    Written12-1999Vaérie Soenen-Cornu, Claude Preudhomme, Jean-Luc Laï, Marc Zandecki, Pierre Fenaux
    Laboratoire d'Hématologie A Hôpital Albert, Calmette - CHRU de Lille, Boulevard du Pr Leclercq 59037, Lille Cedex, France

    Citation

    This paper should be referenced as such :
    Soenen-Cornu, V ; Preudhomme, C ; Lai, JL ; Zandecki, M ; Fenaux, P
    del(17p) in myeloid malignancies
    Atlas Genet Cytogenet Oncol Haematol. 1999;3(4):198-201.
    Free online version   Free pdf version   [Bibliographic record ]
    URL : http://AtlasGeneticsOncology.org/Anomalies/del17pID1142.html

    © Atlas of Genetics and Cytogenetics in Oncology and Haematology
    indexed on : Fri Sep 5 13:08:28 CEST 2014


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