ABNORMALNOSTI HROMOZOMA 8 KOD BOLESNIKA SA PRIMARNIM MIJELODISPLASTIČNIM SINDROMIMA: KLINIČKI I BIOLOŠKI ZNAČAJ

Abstract

INTRODUCTION Rearrangements of any single chromosome in human karyotype have been reported in patients with pMDS.

OBJECTIVE To examine the role of aberrations of chromosome 8 in pathogenesis, clinical presentation and progression of myelodysplastic syndromes.

METHOD Cytogenetic analysis of bone marrow cells was carried out by direct method and by means of 24- and/or 48-hour unstimulated cell culture. Chromosomes were obtained by modified method of HG-bands.

RESULTS On presentation, 109 out of 271 successfully karyotyped patients (40,2%) had abnormal karyotypes. Among them, 22 patients (10.9%) had aberrations of chromosome 8. Ten patients had trisomy 8 as “simple” aberration whilst additional three cases had trisomy 8 included in “complex” karyotypes (≥3 chromosomes). Cases with constitutional trisomy 8 mosaicism (CT8M) were excluded using the chromosome analyses of PHA-stimulated blood cultures. On the contrary, monosomy (seven patients) or deletion of chromosome 8 (two patients) were exclusively found in ”complex” karyotypes. During prolonged cytogenetic follow-up, trisomy 8 was not recorded in evolving karyotypes. In contrast, trisomy 8 disappeared in two cases during subsequent cytogenetic studies, i.e. 23 and 72 months from diagnosis, accompanied in one patient with complete hematological remission. No difference regarding age, sex, cytopenia, blood and marrow blast count or response to treatment was found between patients with trisomy 8 as the sole aberration compared to those with normal cytogenetics. Median survival of patients with trisomy 8 as the sole aberration was 27 months, as compared to 32 months in patients with normal cytogenetics (p=0.468), whilst median survival of patients with aberrations of chromosome 8 included in ”complex” karyotypes was only 4 months.

CONCLUSION Aberrations of chromosome 8 are common in patients with pMDS. The presence of a clone with trisomy 8 is not always the sign of disease progression or poor prognosis in MDS patients, in contrast to clones with aberrations of chromosome 8 manifesting the loss of genetic material.

Keywords: chromosome 8; aberrations; myelodysplastic syndromes; biology; prognosis; incidence