Različiti citogenetski klonovi nastali tokom lečenja Filadelfija pozitivne hronične mijelodne leukemije inhibitorima tirozin kinaze sa progresijom u Filadelfija negativnu akutnu mijeloidnu leukemiju

  • Marija Denčić-Fekete Clinical Center of Serbia, Clinic for Hematology, Belgrade, Serbia
  • Danijela Leković Clinical Center of Serbia, Clinic for Hematology, Belgrade, Serbia
  • Vesna Djordjević Clinical Center of Serbia, Clinic for Hematology, Belgrade, Serbia
  • Jelica Jovanović Clinical Center of Serbia, Clinic for Hematology, Belgrade, Serbia
  • Biljana Todorić-Živanović Military Medical Academy, Belgrade, Serbia
  • Ljubomir Jaković Clinical Center of Serbia, Clinic for Hematology, Belgrade, Serbia
  • Andrija Bogdanović Clinical Center of Serbia, Clinic for Hematology, Belgrade, Serbia
DOI: https://doi.org/10.2298/VSP180723010D
Ključne reči: leukemija, mijeloidna, hronična, bcr-abl pozitivna;, leukemija, mijelocitna akutna;, kariotip, određivanje;, enzimi, inhibitori;, citogenetika

Sažetak


Uvod. Dodatne kariotipske abnormalnosti u Filadelfija-pozitivnom (Ph+) klonu mogu se javiti tokom progresije hronične mijeloidne leukemije (CML) i često su povezane sa rezistencijom na terapiju tirozin kinaznim inhibitorima (TKI). Ponekad se tokom terapije TKI kariotipske abnormalnosti javljaju i u Filadelfija-negativnim (Ph-) ćelijama, ali ne utiču na progresiju bolesti, izuzev abnormalnosti hromozoma 7. Prikaz bolesnika. Kod bolesnice u hroničnoj fazi CML, tokom lečenja TKI uočene su kariotipske abnormalnosti prisutne u tri nezavisna klona sa evolucijom bolesti u akutnu mijeloidnu leukemiju (AML). Primarni Ph+ klon je otkriven tokom hronične faze CML i započeta je terapija imatinib mesilatom. Nakon tri godine hematološke i citogenetske remisije, uočena je evolucija primarnog klona. Započeta je terapija nilotinibom koja je dovela do molekularnog odgovora i povlačenja Ph+ klona sa dodatnim aberacijama, ali i pojavljivanja novog Ph- klona sa trizomijom 8. Nakon 5,5 godina lečenja nilotinibom i postizanja kompletnog molekularnog odgovora, uočen je Ph- klon sa monozomijom 7. Fluorescentna in situ hibridizacija (FISH) pokazala je odsustvo trizomije 8 i prisustvo monozomije 7. Istovremeno, registrovan je porast broja blasta u koštanoj srži i ubrzo je postavljena dijagnoza sekundarne AML. Zaključak. Postizanje kompletnog molekularnog odgovora primenom TKI terapije ne treba da isključi redovno citogenetsko testiranje koštane srži bolesnika sa CML. Otkrivanje kariotipskih abnormalnosti sa lošom prognozom je od velikog značaja zbog mogućnosti razvoja sekundarnih maligniteta – mijelodisplastičnog sindroma i AML.

Reference

Baccarani M, Deininger MW, Rosti G, Hochhaus A, Soverini S, Apperley JF, et al. European LeukemiaNet recommendations for the management of chronic myeloid leukemia: 2013. Blood 2013; 122(6): 872‒84.

Deininger MW, Cortes J, Paquette R, Park B, Hochhaus A, Bacca-rani M, et al. The prognosis for patients with chronic myeloid leukemia who have clonal cytogenetic abnormalities in Phila-delphia chromosome-negative cells. Cancer 2007; 110(7): 1509-19.

Perel JM, McCarthy C, Walker O, Irving I, Williams B, Kennedy GA. Clinical significance of development of Philadelphia chromosome negative clones in patients with chronic myeloid leukemia treated with imatinib mesylate. Haematologica 2005; 90 (Suppl): ECR25.

Bacher U, Hochhaus A, Berger U, Hiddemann W, Hehlmann R, Haferlach T, et al. Clonal aberrations in Philadelphia chromo-some negative hematopoiesis in patients with chronic myeloid leukemia treated with imatinib or interferon alpha. Leukemia 2005; 19(3): 460‒3.

Kovitz C, Kantarjian H, Garcia-Manero G, Abruzzo LV, Cortes J. Myelodysplastic syndromes and acute leukemia developing af-ter imatinib mesylate therapy for chronic myeloid leukemia. Blood 2006; 108(8): 2811‒3.

Terre C, Eclache V, Rousselot P, Imbert M, Charrin C, Gervais C, et al. Report of 34 patients with clonal chromosomal abnor-malities in Philadelphia negative cells during imatinib treat-ment of Philadelphia-positive chronic myeloid leukemia. Leu-kemia 2004; 18(8): 1340-6.

Andersen MK, Pedersen-Bjergaard J, Kjeldsen L, Dufva IH, Brøn-dum-Nielsen K. Clonal Ph-negative hematopoiesis in CML after therapy with imatinib mesylate is frequently characterized by trisomy 8. Leukemia 2002; 16(8): 1390–1393.

Chomczynski P, Sacchi N. Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extrac-tion. Anal Biochem 1987; 162(1): 156‒9.

Moravcová J, Lukásová M, Starý J, Haskovec C. Simple competi-tive two-step RT-PCR assay to monitor minimal residual dis-ease in CML patients after bone marrow transplantation. Leu-kemia 1998; 12(8): 1303‒12.

Denčić-Fekete M, Đorđević V, Storlazzi C. T, Janković G, Bogdanov-ić A, Jovanović J, et al. t(5;6;12) associated with resistance with imatinib mesylate in chronic myeloid leukemia. Int J Hematol 2009; 89(4): 508‒12.

Storlazzi CT, Albano F, Dencić-Fekete M, Djordjević V, Rocchi M. Late-appearing pseudocentric fission event during chronic my-eloid leukemia progression. Cancer Genet Cytogenet 2007; 174(1): 61‒7.

Baldazzi C, Luatti S, Marzocchi G, Stacchini M, Gamberini C, Castagnetti F, et al. Emergence of clonal chromosomal abnor-malities in Philadelphia negative hematopoiesis in chronic my-eloid leukemia patients treated with nilotinib after failure of imatinib therapy. Leukemia Res 2009; 33(12): e218‒20.

Ribeiro de Mello Conchon M, Bendit I, Ferreira P, Lima W, Kumeda C, Dias L, et al. Emergence of abnormal clone with monosomy 7 in Philadelphia negative cells of CML patients treated with tyrosine kinase inhibitors. Int J Hematol 2009; 89(1): 123‒5.

McMullin MF, Humphreys M, Byrne J, Russell NH, Cuthbert RJ, O’Dwyer ME. Chromosomal abnormalities in Ph- cells of pa-tients on imatinib. Blood 2003; 102(7): 2700‒1; author reply 2701.

Bumm T, Müller C, Al-Ali HK, Krohn K, Shepherd P, Schmidt E, et al. Emergence of clonal cytogenetic abnormalities in Ph- cells in some CML patients in cytogenetic remission to imatinib but restoration of polyclonal hematopoiesis in the majority. Blood 2003; 101(5): 1941‒9.

Kharbanda S, Pandey P, Jin S, Inoue S, Bharti A, Yuan ZM, et al. Functional interaction between DNA-PK and c-Abl in re-sponse to DNA damage. Nature 1997; 386(6626): 732‒5.

Fabarius A, Haferlach C, Müller M, Erben P, Lahaye T, Giehl M, et al. Dynamics of cytogenetic aberrations in Philadelphia chromosome positive and negative hematopoiesis during da-satinib therapy of chronic myeloid leukemia patients after imatinib failure. Haematologica 2007; 92(6): 834‒7.

Tanaka H, Tanaka K, Oguma N, Ito K, Ito T, Kyo T, et al. Effect of interferon-α on chromosome abnormalities in treated chronic myelogenous leukemia patients. Cancer Genet Cyto-genet 2004; 153(2): 133‒43.

Groves MJ, Sales M, Baker L, Griffiths M, Pratt N, Tauro S. Fac-tors influencing a second myeloid malignancy in patients with Philadelphia-negative -7 or del(7q) clones during tyrosine ki-nase inhibitor therapy for chronic myeloid leukemia. Cancer Genet 2011; 204(1): 39‒44.

Objavljeno
2021/02/11
Broj časopisa
Vol. 78 Br. 1 (2021): Vojnosanitetski Pregled
Rubrika
Prikaz bolesnika