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  • 1 Dél-pesti Centrumkórház, Országos Hematológiai és Infektológiai Intézet, Budapest
  • 2 Dél-pesti Centrumkórház, Országos Hematológiai és Infektológiai Intézet, 1097 Budapest, Albert Flórián út 5–7.
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Absztrakt:

A mielodiszpláziás szindrómák (MDS) a leggyakoribb hematológiai megbetegedések közé tartoznak, különös tekintettel az idősödő populációkra. Közös jellemzőjük az ineffektív hemopoézis és következményes citopéniák, valamint az akut leukémiába történő transzformáció jelentős esélye. A citogenetikai vizsgálat az MDS diagnózisa felállításának egyik sarokköve, fontos prognosztikai jelentőséggel. Az egyes citogenetikai eltérések orvosi ismerete fontos terápiás következményekkel bír: a lenalidomid hatékony terápiás eszközünk 5q- okozta anémia és esetleg 13-as triszómia esetén. Ugyanakkor 3q- eltérés azonosítása esetén átlagon felüli hatást várhatunk a demetiláló azacitidin- vagy decitabin-terápiától, míg 8-as triszómia és hipocellularitás esetén megfontolandó az immunszuppresszív kezelés alkalmazása. Összefoglalónkkal segítő kezet szeretnénk nyújtani az MDS jobb megismerésén keresztül e betegség eredményesebb gyógykezeléséhez.

  • 1

    Vallespi T, Imbert M, Mecucci C, et al. Diagnosis, classification, and cytogenetics of myelodysplastic syndromes. Haematologica 1998; 83: 258–275.

  • 2

    Malcovati L, Hellstrom-Lindberg E, Bowen D, et al. Diagnosis and treatment of primary myelodysplastic syndromes in adults: recommendations from the European LeukemiaNet. Blood 2013; 122: 2943–2964.

  • 3

    Greenberg PL, Tuechler H, Schanz J, et al. Revised international prognostic scoring system for myelodysplastic syndromes. Blood 2012; 120: 2454–2465.

  • 4

    Schanz J, Tuchler H, Sole F, et al. New comprehensive cytogenetic scoring system for primary myelodysplastic syndromes (MDS) and oligoblastic acute myeloid leukemia after MDS derived from an international database merge. J Clin Oncol. 2012; 30: 820–829.

  • 5

    Kanagal-Shamanna R, Hodge JC, Tucker T, et al. Assessing copy number aberrations and copy neutral loss of heterozygosity across the genome as best practice: An evidence based review of clinical utility from the cancer genomics consortium (CGC) working group for myelodysplastic syndrome, myelodysplastic/myeloproliferative and myeloproliferative neoplasms. Cancer Genet. 2018.

  • 6

    Montalban-Bravo G and Garcia-Manero G. Myelodysplastic syndromes: 2018 update on diagnosis, risk-stratification and management. Am J Hematol. 2018; 93: 129–147.

  • 7

    Mossner M, Jann JC, Nowak D, et al. Prevalence, clonal dynamics and clinical impact of TP53 mutations in patients with myelodysplastic syndrome with isolated deletion (5q) treated with lenalidomide: results from a prospective multicenter study of the german MDS study group (GMDS). Leukemia 2016; 30: 1956–1959.

  • 8

    Ebert BL Molecular dissection of the 5q deletion in myelodysplastic syndrome. Semin Oncol. 2011; 38: 621–626.

  • 9

    Ebert BL, Pretz J, Bosco J, et al. Identification of RPS14 as a 5q- syndrome gene by RNA interference screen. Nature 2008; 451: 335–339.

  • 10

    Starczynowski DT, Kuchenbauer F, Argiropoulos B, et al. Identification of miR-145 and miR-146a as mediators of the 5q- syndrome phenotype. Nat Med. 2010; 16: 49–58.

  • 11

    Schneider RK, Adema V, Heckl D, et al. Role of casein kinase 1A1 in the biology and targeted therapy of del(5q) MDS. Cancer Cell. 2014; 26: 509–520.

  • 12

    Bello E, Pellagatti A, Shaw J, et al. CSNK1A1 mutations and gene expression analysis in myelodysplastic syndromes with del(5q). Br J Haematol. 2015; 171: 210–214.

  • 13

    Steensma DP. Myelodysplastic syndromes current treatment algorithm 2018. Blood Cancer J. 2018; 8: 47.

  • 14

    Braulke F, Schulz X, Germing U, et al. Peripheral blood cytogenetics allows treatment monitoring and early identification of treatment failure to lenalidomide in MDS patients: results of the LE-MON-5 trial. Ann Hematol. 2017; 96: 887–894.

  • 15

    Wei S, Chen X, McGraw K, et al. Lenalidomide promotes p53 degradation by inhibiting MDM2 auto-ubiquitination in myelodysplastic syndrome with chromosome 5q deletion. Oncogene 2013; 32: 1110–1120.

  • 16

    Wei S, Chen X, Rocha K, et al. A critical role for phosphatase haplodeficiency in the selective suppression of deletion 5q MDS by lenalidomide. Proc Natl Acad Sci. U S A 2009; 106: 12974v12979.

  • 17

    Fang J, Liu X, Bolanos L, et al. A calcium- and calpain-dependent pathway determines the response to lenalidomide in myelodysplastic syndromes. Nat Med. 2016; 22: 727–734.

  • 18

    Arora M, Gowda S, and Tuscano J. A comprehensive review of lenalidomide in B-cell non-Hodgkin lymphoma. Ther Adv Hematol. 2016; 7: 209–221.

  • 19

    Payne EM, Virgilio M, Narla A, et al. L-Leucine improves the anemia and developmental defects associated with Diamond-Blackfan anemia and del(5q) MDS by activating the mTOR pathway. Blood 2012; 120: 2214–2224.

  • 20

    Bello E, Kerry J, Singh S, et al. L-leucine increases translation of RPS14 and LARP1 in erythroblasts from del(5q) myelodysplastic syndrome patients. Haematologica 2018; 103: e496–e500.

  • 21

    Inaba T, Honda H, and Matsui H. The enigma of monosomy 7. Blood 2018; 131: 2891–2898.

  • 22

    Arthur RK, An N, Khan S, et al. The haploinsufficient tumor suppressor, CUX1, acts as an analog transcriptional regulator that controls target genes through distal enhancers that loop to target promoters. Nucleic Acids Res. 2017; 45: 6350–6361.

  • 23

    McNerney ME, Brown CD, Wang X, et al. CUX1 is a haploinsufficient tumor suppressor gene on chromosome 7 frequently inactivated in acute myeloid leukemia. Blood 2013; 121: 975–983.

  • 24

    Heuser M, Yap DB, Leung M, et al. Loss of MLL5 results in pleiotropic hematopoietic defects, reduced neutrophil immune function, and extreme sensitivity to DNA demethylation. Blood 2009; 113: 1432–1443.

  • 25

    Sebert M, Komrokji RS, Sekeres MA, et al. Impact of baseline cytogenetic findings and cytogenetic response on outcome of high-risk myelodysplastic syndromes and low blast count AML treated with azacitidine. Leuk Res. 2017; 63: 72–77.

  • 26

    Sloand EM, Pfannes L, Chen G, et al. CD34 cells from patients with trisomy 8 myelodysplastic syndrome (MDS) express early apoptotic markers but avoid programmed cell death by up-regulation of antiapoptotic proteins. Blood 2007; 109: 2399–2405.

  • 27

    Drevon L, Marceau A, Maarek O, et al. Myelodysplastic syndrome (MDS) with isolated trisomy 8: a type of MDS frequently associated with myeloproliferative features? A report by the Groupe Francophone des Myelodysplasies. Br J Haematol. 2018; 182: 843–850.

  • 28

    Sloand EM, Mainwaring L, Fuhrer M, et al. Preferential suppression of trisomy 8 compared with normal hematopoietic cell growth by autologous lymphocytes in patients with trisomy 8 myelodysplastic syndrome. Blood 2005; 106: 841–851.

  • 29

    Wesner N, Drevon L, Guedon A, et al. Inflammatory disorders associated with trisomy 8-myelodysplastic syndromes: French retrospective case-control study. Eur J Haematol. 2018.

  • 30

    Bacher U, Haferlach T, Schnittger S, et al. Investigation of 305 patients with myelodysplastic syndromes and 20q deletion for associated cytogenetic and molecular genetic lesions and their prognostic impact. Br J Haematol. 2014; 164: 822–833.

  • 31

    Huh J, Tiu RV, Gondek LP, et al. Characterization of chromosome arm 20q abnormalities in myeloid malignancies using genome-wide single nucleotide polymorphism array analysis. Genes Chromosomes Cancer 2010; 49: 390–399.

  • 32

    Nomdedeu M, Pereira A, Calvo X, et al. Clinical and biological significance of isolated Y chromosome loss in myelodysplastic syndromes and chronic myelomonocytic leukemia. A report from the Spanish MDS Group. Leuk Res. 2017; 63: 85–89.

  • 33

    Ganster C, Kampfe D, Jung K, et al. New data shed light on Y-loss-related pathogenesis in myelodysplastic syndromes. Genes Chromosomes Cancer 2015; 54: 717–724.

  • 34

    Abruzzese E, Rao PN, Slatkoff M, et al. Monosomy X as a recurring sole cytogenetic abnormality associated with myelodysplastic diseases. Cancer Genet Cytogenet. 1997; 93: 140–146.

  • 35

    Bacher U, Schanz J, Braulke F, et al. Rare cytogenetic abnormalities in myelodysplastic syndromes. Mediterr J Hematol Infect Dis. 2015; 7: e2015034.

  • 36

    Laricchia-Robbio L, Premanand K, Rinaldi CR, et al. EVI1 Impairs myelopoiesis by deregulation of PU.1 function. Cancer Res. 2009; 69: 1633–1642.

  • 37

    Senyuk V, Sinha KK, Li D, et al. Repression of RUNX1 activity by EVI1: a new role of EVI1 in leukemogenesis. Cancer Res. 2007; 67: 5658–5666.

  • 38

    Wanquet A, Prebet T, Berthon C, et al. Azacitidine treatment for patients with myelodysplastic syndrome and acute myeloid leukemia with chromosome 3q abnormalities. Am J Hematol. 2015; 90: 859–863.

  • 39

    Mesa RA, Hanson CA, Ketterling RP, et al. Trisomy 13: prevalence and clinicopathologic correlates of another potentially lenalidomide-sensitive cytogenetic abnormality. Blood 2009; 113: 1200–1201.

  • 40

    Silva FP, Lind A, Brouwer-Mandema G, et al. Trisomy 13 correlates with RUNX1 mutation and increased FLT3 expression in AML-M0 patients. Haematologica 2007; 92: 1123–1126.

  • 41

    Fehniger TA, Byrd JC, Marcucci G, et al. Single-agent lenalidomide induces complete remission of acute myeloid leukemia in patients with isolated trisomy 13. Blood 2009; 113: 1002–1005.

  • 42

    Kanagal-Shamanna R, Bueso-Ramos CE, Barkoh B, et al. Myeloid neoplasms with isolated isochromosome 17q represent a clinicopathologic entity associated with myelodysplastic/myeloproliferative features, a high risk of leukemic transformation, and wild-type TP53. Cancer. 2012; 118: 2879–2888.

  • 43

    Kanagal-Shamanna R, Luthra R, Yin CC, et al. Myeloid neoplasms with isolated isochromosome 17q demonstrate a high frequency of mutations in SETBP1, SRSF2, ASXL1 and NRAS. Oncotarget. 2016; 7: 14251–14258.

  • 44

    Lamprianidou E, Kordella C, Papoutselis M, et al. Myeloid Neoplasms with Isolated Isochromosome 17q: a yet to be Defined Entity. Mediterr J Hematol Infect Dis. 2017; 9: e2017066.

  • 45

    Haase D, Germing U, Schanz J, et al. New insights into the prognostic impact of the karyotype in MDS and correlation with subtypes: evidence from a core dataset of 2124 patients. Blood 2007; 110: 4385–4395.

  • 46

    Arber DA, Orazi A, Hasserjian R, et al. The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia. Blood 2016; 127: 2391–2405.