Author/Editor		Pajič, Tadej; Černelč, Peter
Title		Kronična mieloična levkemija in molekularno genetični načini ugotavljanja bolezni
Translated title		Chronic myeloid leukaemia and respondent molecular diagnostic methods
Type		članek
Source		Zdrav Vestn
Vol. and No.		Letnik 67, št. Suppl 1
Publication year		1998
Volume		str. I-69-72
Language		slo
Abstract		Chronic myeloid leukaemia (CML) is a clonal myeloproliferative disorder resulting from the neoplastic transformation of the primitive hemopoietic stem cell. The Philadelphia chromosome (Ph chromosome) was the first described consistent chromosome aberration identified in CML in 1960. THe shortness chromosome 22 is a product of a reciprocal translocation involving the long arm (q) of chrosome 9, band 34, and band q11 of chromosome 22, (t(9;22) (q34;q11). Molecular analysis has localized the breakpoint on chromosome 9 to proto-oncogene ABL, and the breakpoint on chromosome 22 to BCR gene. The t(9;22) (q34;q11) results in the formation of two bybrid genes, BCR-ABL on the Ph chromosome and ABL-BCR on 9q+. The hybrid BCR-ANL gene encodes a chimeric protein with a molecular weight of 210 kd (p210BCR/ABL) which is associated with the uncontrolled proliferation of the leukaemic cells in the CML. The role of the ABL-BCR fusion gene remains unknown. For the great majority of patients with CML, the Ph chromosome is a specific marker of the malignant clone that can be detected by different methods. The standard cytogenetic and also sensitive and specific molecular methods like Southern blotting and resverse transcriptase - polymerase chain reaction (RT-PCR) can be used in the diagnosis and followup of the minimal residual disease in the CML patients. Using Southern blotting, a rearrangement is detectable in more than 95% of Ph-positive cases and also in a significant proportion of Ph-negative cases. RT-PCR is by far the most sensitive assay and is most appropiate for monitoring patients who are in complete cytogenetic remission.
Summary		Kronična mieloična levkemija (KML) je klonska mieloproliferativna bolezen, ki nastane z neoplastično preobrazbo maličnih krvotvornih celic. Kromosom Philadelphia je prva opisana kromosomska nepravilnost, ki so jo leta 1960 ugotovili pri KML. Ta skrajšani kromosom 22 nastane z recipročno translokacijo med končnim segmentom 34 dolgega kraka (q) kromosoma 9 in segmentom q11, kromosoma 22 (t(9;22) (q34;q11). Prelomno mesto je na kromosomu 9 znotraj proto-onkogena ABL, na kromosomu 22 pa znotraj gena BCR. Posledica translokacije t(9;22) (q34;q11) je trorba hibridnega gena BCR-ABL na Ph kromosomu in gena ABL-BCR na 9q+kromosomu. Hibridni gen BCR-ABL označuje himerični protein z molekularno maso 210 kd (p210BCR/ABL), ki ga povezujejo z nekontrolirano proliferacijo levkemičnih celic pri KML. Vloga gena ABL-BCR pri KML ostaja nejasna. Za veliko večino bolnikov s KML je kromosom Philadelphia specifični označevalec neoplastičnega klona, ki ga ugotavljamo z različnimi metodami. Ob standardnih citogenetičnih metodah se pri ugotavljanju bolezni in spremljanju minimalnega preostalega klona levkemičnih celic po zdravljenju uporabljajo tudi zelo občutljive in specifične molekularno genetične metode kot sta hibridizacija po Southernu in reverzno transkripcijska verižna reakcija polimerizacije. Z metodo hibridizacije po Southernu je mogoče ugotoviti več kot 95% kromosom Ph pozitivnih in tudi velik del kromosom Ph negativnih bolnikov s KML. Reverzno transkripcijska verižna reakcija polimerizacije je izmed najobčutljivejša metoda in je najprimernejša za spremljanje bolnikov s KML v popolni citogenetični remisiji po zdravljenju.
Descriptors		LEUKEMIA, MYELOID, CHRONIC PHILADELPHIA CHROMOSOME RNA-DIRECTED DNA POLYMERASE RANDOM AMPLIFIED POLYMORPHIC DNA TECHNIQUE NUCLEIC ACID HYBRIDIZATION