Zbornik - Društvo genetičara Srbije

V-Uvo-2 ZBORNIK ABSTRAKATA III KONGRESA GENETIÈARA SRBIJE 181
Subotica, 30. novembar - 4. decembar 2004.
CITOGENETSKI I MOLEKULARNI PROFIL HRONIÈNE
MIJELOIDNE LEUKEMIJE
Biljana Todoriæ-ivanoviæ, Dragana Stamatoviæ, Milica Strnad,
1
Koviljka Krtolica i Z. Magiæ
Vojnomedicinska Akademija, Beograd
1
Institut za nuklearne nauke «Vinèa», Beograd
Hronièna mijeloidna leukemija (CML) predstavlja klonalnu bolest matiène æelije
hematopoeze. U preko 90% sluèajeva karakteriše se prisustvom Philadelphia (Ph)
hromozoma nastalog reciproènom translokacijom t(9;22)(q34;q11). Ph hromozom
predstavlja prvu hromozomsku aberaciju povezanu sa malignim oboljenjem kod ljudi. U
5-10% sluèajeva Ph hromozom nastaje rearanmanima drugaèijim od klasiène t(9;22).
To su varijantne Ph translokacije. U 5-10% bolesnika Ph hromozom nije prisutan.
Translokacijom t(9;22)(q34;q11) æelijski protonkogen c-abl smešten u 9q34 spaja se sa
bcr genom smeštenim u 22q11 i formira himerni bcr-abl gen koji kodira protein sa
poveæanom tirozin kinaznom aktivnošæu. Smatra se da upravo ovaj protein ima centralnu
ulogu u patogenezi CML. U najveæem broju sluèajeva formira se jedan od dva tipa
bcr-abl rearanmana b3a2 ili b2a2. Cilj ovoga rada bio je da se citogenetski ispitaju
bolesnici sa CML kao i da se utvrdi uèestalost formi bcr-abl gena. Citogenetski je
ispitana grupa od 141 bolesnika sa CML. Nakon preparacije hromozoma iz koštane sri
direktnom metodom i/ili nakon 24h kulture, citogenetski je analizirano 20 metafaza.
RNK je izolovana iz mononuklearnih æelija periferne krvi. RT-PCR metoda raðena je sa
prajmerima za bcr-abl sekvencu. Klasièna t(9;22)(q34;q11) detektovana je kod 122
(86.5%) bolesnika. Varijantne Ph translokacije kod 6 (4.3%) bolesnika. Normalan
kariotip kod 13 (9.3%), 1 bolesnik je bio Ph negativan i bcr-abl negativan. U grupi od 47
bolesnika sa CML kod koje je utvrðeno prisustvo bcr-abl gena, b3a2 forma detektovana
je kod 36 (76.6%) a b2a2 forma kod 11 (23.4%). Podaci dobijeni citogenetskim i
molekularnim ispitivanjima naše grupe bolesnika poklapaju se sa podacima iz literature.
CYTOGENETIC AND MOLECULAR PROFILE OF
CHRONIC MYELOID LEUKEMIA
Chronic myeloid leukemia (CML) is a clonally myeloproliferative disease of the
pluripotent stem cell. Characteristic of the disease is a presence of Philadelphia (Ph)
chromosome produced by reciprocal translocation t(9;22)(q34;q11) in more than 90% of
the cases. Ph chromosome was the first consistent chromosome abnormality detected in a
human malignance. The Ph chromosome originates through other rearrangements than
the classic t(9;22) in 5-10% of CML cases. Those are variant Ph translocations. The Ph
chromosome is absent in 5-10% of cases. Cell proto-oncogene c-abl located at 9q34 is
fussed with bcr located at 22q11 by this translocation t(9;22)(q34;q11). Chimeric bcr-abl
gene is coding protein with elevated tyrosine kinase activity. It is taught that this protein
plays central role in pathogenesis of the CML. In the largest number of cases one of the
two types of bcr-abl gene is formed: b3a2 and b2a2. The aim of this study was
cytogenetic investigation of the group of CML patients and molecular investigation of
the frequency of bcr-abl forms. We cytogenetically investigated the group of 141 patients
(pts) with CML. Chromosomes were preparated from bone marrow aspirates by the direct
method or/and after 24h culture. We analyzed 20 metaphases of each patient. RNA
was isolated from peripheral blood mononuclear cells. RT-PCR method was done with
primers for bcr-abl sequence. Classic t(9;22)(q34;q11) was detected in 122 (86.5%) pts,
variant Ph translocation in 6 (4.3%) pts, normal karyotipe in 13 (9.3%), and one patient
was Ph negative and bcr-abl negative. In the group of 47 CML pts who were bcr-abl positive,
b3a2 form was detected in 36 (76.6%) pts and b2a2 in 11 (23.4%). Resultates from
this study are in correlation with resultates obtained from the literature.