title: Evolution of Tumor Clones in Adult Acute Lymphoblastic Leukemia.
abstract: Clonal instability of a tumor cell population in acute lymphoblastic leukemia (ALL) may complicate the monitoring of a minimal residual disease (MRD) by means of patient-specific targets identified at the disease onset. Most of the data concerning the possible instability of rearranged clonalTCRandIGgenes during disease recurrence were obtained for ALL in children. The appropriate features of adult ALL, which are known to differ from those of childhood ALL in certain biological characteristics and prognosis, remain insufficiently studied. The aim of this study was to assess the stability ofIGandTCRgene rearrangements in adult ALL. Rearrangements were identified according to the BIOMED-2 protocol (PCR followed by fragment analysis). Mismatch in clonal rearrangements at onset and relapse was identified in 83% of patients, indicating clonal instability during treatment. Clonal evolution and diversity ofIGandTCRgene rearrangements may be one of the tumor progression mechanisms. New rearrangements may emerge due to residual VDJ-recombinase activity in tumor cells. Also, many clonalIGandTCRgene rearrangements may be present at different levels at a diagnosis, but less abundant clones may be "invisible" due to limited detection sensitivity. Later, major clones may disappear in the course of chemotherapy, while others may proliferate. Investigation of clonal evolution and heterogeneity in ALL and their impact on the treatment efficacy will contribute to the identification of new prognostic factors and the development of therapeutic approaches.
authors.affiliation: National Hematology Research Center, Novy Zykovskiy Proezd, 4a, Moscow, 125167, Russia.
authors.forename: S Yu
authors.initials: SY
authors.lastname: Smirnova
authors.affiliation: National Hematology Research Center, Novy Zykovskiy Proezd, 4a, Moscow, 125167, Russia.
authors.forename: Yu V
authors.initials: YV
authors.lastname: Sidorova
authors.affiliation: National Hematology Research Center, Novy Zykovskiy Proezd, 4a, Moscow, 125167, Russia.
authors.forename: N V
authors.initials: NV
authors.lastname: Ryzhikova
authors.affiliation: Faculty of Basic Medicine, Lomonosov Moscow State University, Lomonosov Ave., 31/5, Moscow, 119192, Russia.
authors.forename: K A
authors.initials: KA
authors.lastname: Sychevskaya
authors.affiliation: National Hematology Research Center, Novy Zykovskiy Proezd, 4a, Moscow, 125167, Russia.
authors.forename: E N
authors.initials: EN
authors.lastname: Parovichnikova
authors.affiliation: National Hematology Research Center, Novy Zykovskiy Proezd, 4a, Moscow, 125167, Russia.
authors.forename: A B
authors.initials: AB
authors.lastname: Sudarikov
keywords: IG and TCR gene rearrangements; acute lymphoblastic leukemia; relapse