title: Survivin and P-glycoprotein are associated and highly expressed in late phase chronic myeloid leukemia.
abstract: Resistance to tyrosine-kinase inhibitors is a serious problem in the treatment of chronic myeloid leukemia (CML). Using Western blot, real-time qRT-PCR and flow cytometry, we investigated the expression of survivin, Smac/DIABLO and P-glycoprotein (Pgp) in patients with CML. Survivin overexpression has been associated with cancer progression, multidrug resistance, poor prognosis and short survival in several types of neoplasms including hematological malignancies. In this work, survivin expression was significantly elevated in late, in contrast to early, chronic phase CML (p=0.044). Patients with high or intermediate prognostic Sokal score presented higher survivin levels (p=0.012), as well as Smac/DIABLO levels (p=0.009) compared to low Sokal score. The strong correlation between survivin and Pgp expression in late (p=0.018), but not in early (p=0.5) chronic phase of CML, suggests that this association may play a biological role in late CML phase and may offer an important target for the development of new therapies.
authors.affiliation: Laboratório de Hemato-Oncologia Celular e Molecular, Programa de Pesquisa em Hemato-Oncologia Molecular, Instituto Nacional de Câncer Rio de Janeiro, RJ, Brazil.
authors.forename: Flaviana R S
authors.initials: FR
authors.lastname: Reis
authors.forename: Flavia C
authors.initials: FC
authors.lastname: Vasconcelos
authors.forename: Débora L
authors.initials: DL
authors.lastname: Pereira
authors.forename: Arthur
authors.initials: A
authors.lastname: Moellman-Coelho
authors.forename: Karina L
authors.initials: KL
authors.lastname: Silva
authors.forename: Raquel C
authors.initials: RC
authors.lastname: Maia
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000096:biosynthesis* / Q000235:genetics; D000328:Adult; D051017:Apoptosis Regulatory Proteins; D015153:Blotting, Western; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000096:biosynthesis* / Q000235:genetics; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics; D020014:K562 Cells; D015466:Leukemia, Myeloid, Chronic-Phase / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D024101:Mitochondrial Proteins / Q000096:biosynthesis / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000077022:Survivin; D055815:Young Adult
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D051017:Apoptosis Regulatory Proteins; C107489:BIRC5 protein, human; C412403:DIABLO protein, human; D051034:Inhibitor of Apoptosis Proteins; D047908:Intracellular Signaling Peptides and Proteins; D024101:Mitochondrial Proteins; D012333:RNA, Messenger; D000077022:Survivin