Slobodanka Ostojić

Bone morphogenetic proteins and receptors are over-expressed in bone-marrow cells of multiple myeloma patients and support myeloma cells by inducing ID genes

We assessed the expression pattern and clinical relevance of BMPs and related molecules in multiple myeloma (MM). MM bone-marrow samples (n=32) had increased BMP4, BMP6, ACVR1 and ACVR2A, and decreased NOG expression compared with controls (n=15), with BMP6 having the highest sensitivity/specificity. Within MM bone-marrow, the source of BMPs was mainly CD138(+) plasma-cell population, and BMP6 and ACVR1 expression correlated with plasma-cell percentage. Using myeloma cell lines NCI H929 and Thiel we showed that BMPs induced ID1, ID2 and IL6, and suppressed CDKN1A and BAX gene expression, and BAX protein expression. Finally, BMPs partially protected myeloma cells from bortezomib- and TRAIL-induced apoptosis. We concluded that BMPs may be involved in MM pathophysiology and serve as myeloma cell biomarkers.

Exacerbation of Psoriasis after Treatment with Alpha-Interferon

Rajko Kušec, MD, Slobodanka Ostojić, MD, Ana Planinc-Peraica, MD, Hrvoje Minigo, MD Branimir Jakšić, MD, PhD, Department of Hematology, Clinical Hospital ‘O Novosel’ Zajčeva 19, 41000 Zagreb (Yugoslavia) Dear Sir, At the International Symposium on Interferons and Related Lym-phokines held in Berlin 1989, Harrison [1] described the exacerbation of psoriasis after treatment with α-interferon. As we have observed a similar behaviour of the psoriatic process under treatment with α-interferon we would like to briefly present our experience with a comment on the possible explanation for this phenomenon. We have treated a 54-year-old male patient with hairy cell leukaemia and psoriasis with recombinant α2b-interferon. Therapy with α-interferon (Intron A; Schering) in doses of 3 MU s.c. thrice weekly was started because of the activation of malignant disease. The condition had been stable previously for 9 years not requiring specific or supportive therapy (splenec-tomy was performed early at the time of diagnosis). A psoriasis with skin and joint involvement was established 3 years from the diagnosis of hairy cell leukaemia. The disease was stationary with usual topical therapy and occasionally nonsteroid analgesics. A month after starting α-interferon treatment, which was already showing haematological improvement, the exacerbation of psoriatic skin manifestations occurred with arthralghias, limitations of movement in affected joints and swelling of small finger joints. This condition did not conform with a pattern of typical interferon-related side-effects. Interferon treatment was discontinued for a month with a substantial improvement of psoriasis entering again a stationary phase. After this period α-interferon was restarted, and again exacerbation of psoriasis was noted. This resulted in the definite exclusion of the patient from αinterferon treatment for hairy cell leukaemia. The cause for this finding is not clear. At the same symposium a study detecting various interferons in psoriatic skin was presented providing data on the presence of α-interferon in the active disease, while it was absent in the stable phase or normal skin [2]. Searching for other mechanisms that could mediate/regulate a psoriatic process, an increased adrenal activity during interferon therapy should be considered [3], which, we believe, deserves further clarification. References Harrison P: Exacerbation of psoriasis with alpha interferon (abstract). J Invest Dermatol 1989;93:555.

The role of microRNA in myelodysplastic syndromes: beyond DNA methylation and histone modification

Myelodysplastic syndromes (MDS) are heterogeneous group of hematologic disorders of mostly elderly and based on distinct clinical phenotypes. Current paradigm of their pathogenesis relies on somatic gene mutations combined with the predisposing defective osteohematopoietic niche, but due to the breakout in epigenetic research scientific focus has steered toward two most common epigenetic modifications: methylation mechanisms and histone modification. At the same time, relatively few studies have been undertaken regarding the third epigenetic pathway – microRNAs – in MDS. The main aim of this review is to provide the basics of microRNA biology and function in oncogenesis, showing the complexity of mechanisms behind this single‐stranded 22 nucleotides long RNA molecule, with further focus on its implication in MDS pathology and clinical context. By extensive literature search, we have shown enough evidence for their deregulation in MDS. However, few studies have addressed the issue on pathogenic events in MDS and its association with specific microRNAs. Preliminary research in clinical setting has shown the possible utility of microRNAs in terms of prognosis and therapy, although we are only beginning to understand various implications of microRNAs in MDS and further extensive research is warranted to answer multiple questions arising from interconnection of this epigenetic mechanism in MDS.