Induced differentiation of leukemia cells is in the focus of basic and applied biomedical studies medicine and biology for more than 30 years. During this period specific regulatory molecules involved in the maturation process have been identified by biochemical and molecular biological methods. Recent developments of high-throughput transcriptomic and proteomic techniques made it possible to analyze large sets of mRNA and proteins; this resulted in identification of functionally important signal transduction pathways and networks of molecular interactions, and thus extent existing knowledge on the molecular mechanisms of induced differentiation. Despite significant advances in mechanisms of induced differentiation, many problems related to the molecular mechanism of cell maturation, a phenomenon of therapeutic resistance of leukemic cells need better understanding and thus require further detailed study. Transcriptomics and proteomics methods provide a suitable methodological platform for the implementation of such studies. This review highlights the use of transcriptomic and proteomic methods in studies aimed at various aspects of the induced differentiation. Special attention is paid to the employment of the systems approach for investigation of various aspects of cell maturation. The use of the systems approach in studies of induced differentiation is an important step for the transition from the formal data accumulation on expression of mRNA and proteins towards creating models of biological processes in silico.
Indutsirovannaia differentsirovka leĭkoznykh kletok iavliaetsia predmetom fundamental'nykh i prikladnykh issledovaniĭ v oblasti meditsiny i biologii bolee 30 let. Za éto vremia s ispol'zovaniem metodov biokhimii i molekuliarnoĭ biologii udalos' vyiavit' otdel'nye reguliatornye molekuly, zadeĭstvovannye v protsesse sozrevaniia kletok. Razvitie vysokoproizvoditel'nykh metodov transkriptomiki i proteomiki sdelalo vozmozhnym analiz bol'shikh sovokupnosteĭ mRNK i belkov, chto pozvolilo vyiavit' funktsional'no znachimye puti signal'noĭ transduktsii i seti mezhmolekuliarnykh vzaimodeĭstviĭ, i tem samym rasshirit' predstavleniia o molekuliarnom mekhanizme indutsirovannoĭ differentsirovki. Nesmotria na znachitel'nye uspekhi v issledovanii indutsirovannoĭ differentsirovki, mnogie voprosy, sviazannye s molekuliarnym mekhanizmom sozrevaniia kletok, fenomenom terapevticheskoĭ rezistentnosti leĭkoznykh kletok, ostaiutsia otkrytymi i trebuiut detal'nogo izucheniia. Metody transkriptomiki i proteomiki predostavliaiut podkhodiashchuiu metodologicheskuiu bazu dlia realizatsii podobnykh issledovaniĭ. Dannyĭ obzor posviashchen primeneniiu transkriptomnykh i proteomnykh metodov dlia issledovaniia razlichnykh aspektov indutsirovannoĭ differentsirovki. Osobogo vnimaniia zasluzhivaet sistemnyĭ podkhod k izucheniiu sozrevaniia kletok. Primenenie sistemnogo podkhoda k issledovaniiu indutsirovannoĭ differentsirovki iavliaetsia vazhnym shagom dlia perekhoda ot formal'noĭ katalogizatsii dannykh ob ékspressii mRNK i belkov k postroeniiu modeleĭ biologicheskikh protsessov in silico.
Keywords: HL60 cell line; induced differentiation; proteomics; systems biology; transcriptomics.