Chronic myelogenous leukemia

Abstract

Chronic myelogenous leukemia (CML) is a rare myeloproliferative disease with an incidence of approximately 1-2/100,000 population per year. It is a clonal disease of a pluripotent stem cell committed to granulopoiesis. Most patients are diagnosed in the chronic phase when the blood count typically shows leukocytosis with predominance of mature neutrophil granulocytes and there are evident signs of increased metabolism, such as fatigue, weight loss and perspiration, and splenomegaly. Through the accelerated phase, the chronic phase progresses to a blast crisis resembling acute leukemia. The diagnosis is based on the discovery of the Philadelphia chromosome arising as a consequence of chromosomal translocation t(9;22), BCRABL gene or its product, BCR-ABL tyrosine kinase, in the peripheral blood or bone marrow cells. Significant progress in the treatment of CML was accomplished by the discovery of the BCR-ABL tyrosine kinase inhibitors, which provide long-term disease control, namely with imatinib as the first choice of treatment in the chronic phase of CML. The other two possible treatments are the allogeneic transplantation of haematopoietic stem cells and palliative treatment with chemotherapeutics.

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Povzetek

Kronična mieloična levkemija (KML) je redka mieloproliferativna bolezen z incidenco okrog 1–2/100.000 prebivalcev na leto. Je klonska bolezen pluripotentne matične celice, usmerjene v granulopoezo. Večino bolnikov odkrijemo v kroničnem obdobju, za katero je značilna levkocitoza v krvni sliki, s prevladovanjem zrelih nevtrofilnih granulocitov, znaki pospešene presnove, kot so utrujenost, hujšanje in potenje, ter splenomegalija. Kronično obdobje prek pospešenega obdobja preide v blastno krizo s sliko akutne levkemije. Za postavitev diagnoze je nujna najdba kromosoma Philadelphia, ki nastane kot posledica kromosomske translokacije t(9;22), gena BCR-ABL ali njegovega produkta tirozinske kinaze BCR- -ABL v celicah periferne krvi ali kostnega mozga.
Velik napredek pri zdravljenju KML je bilo odkritje zaviralcev tirozinske kinaze BCR-ABL, s katerimi dosežemo dolgotrajen nadzor bolezni, in sicer z imatinibom kot prvo izbiro zdravljenja kroničnega obdobja KML. Drugi možni izbiri zdravljenja sta alogenična presaditev krvotvornih matičnih celic in paliativno zdravljenje s kemoterapevtiki.