Abstract:
:DH-JH rearrangements of the Ig heavy-chain gene (IGH) occur early during B-cell development. Consequently, they are detected in precursor-B-cell acute lymphoblastic leukemias both at diagnosis and relapse. Incomplete DJH rearrangements have also been occasionally reported in mature B-cell lymphoproliferative disorders, but their frequency and immunobiological characteristics have not been studied in detail. We have investigated the frequency and characteristics of incomplete DJH as well as complete VDJH rearrangements in a series of 84 untreated multiple myeloma (MM) patients. The overall detection rate of clonality by amplifying VDJH and DJH rearrangements using family-specific primers was 94%. Interestingly, we found a high frequency (60%) of DJH rearrangements in this group. As expected from an immunological point of view, the vast majority of DJH rearrangements (88%) were unmutated. To the best of our knowledge, this is the first systematic study describing the incidence of incomplete DJH rearrangements in a series of unselected MM patients. These results strongly support the use of DJH rearrangements as PCR targets for clonality studies and, particularly, for quantification of minimal residual disease by real-time quantitative PCR using consensus JH probes in MM patients. The finding of hypermutation in a small proportion of incomplete DJH rearrangements (six out of 50) suggests important biological implications concerning the process of somatic hypermutation. Moreover, our data offer a new insight in the regulatory development model of IGH rearrangements.
journal_name
Leukemiajournal_title
Leukemiaauthors
González D,Balanzategui A,García-Sanz R,Gutiérrez N,Seabra C,van Dongen JJ,González M,San Miguel JFdoi
10.1038/sj.leu.2402964subject
Has Abstractpub_date
2003-07-01 00:00:00pages
1398-403issue
7eissn
0887-6924issn
1476-5551pii
2402964journal_volume
17pub_type
杂志文章相关文献
LEUKEMIA文献大全abstract::The LH2 gene encodes a putative transcription factor containing two N-terminal LIM and one C-terminal HOX domains. The LH2 locus was mapped to 9q33-34.1, centromeric to the ABL gene. In a recent report, it was suggested that high levels of LH2 expression are consistently observed in chronic myeloid leukemia (CML) pati...
journal_title:Leukemia
pub_type: 杂志文章
doi:
更新日期:1996-07-01 00:00:00
abstract::The role of endothelial progenitor cell (EPC)-mediated vasculogenesis in hematological malignancies is not well explored. Here, we showed that EPCs are mobilized from the bone marrow (BM) to the peripheral blood at early stages of multiple myeloma (MM); and recruited to MM cell-colonized BM niches. Using EPC-defective...
journal_title:Leukemia
pub_type: 杂志文章
doi:10.1038/leu.2016.3
更新日期:2016-05-01 00:00:00
abstract::max 41 transgenic mice consistently exhibit elevated numbers of mature granulocytes and monocytes in the peripheral blood and of immature and mature cells of these lineages in the marrow, spleen, lymph nodes and liver. The immature populations are not autonomous and exhibit a normal quantitative responsiveness to prol...
journal_title:Leukemia
pub_type: 杂志文章
doi:
更新日期:1996-02-01 00:00:00
abstract::We have investigated the direct effects of interferon (IFN) on hairy cells (HCs) isolated from patients with hairy cell leukemia using one- and two-dimensional gel electrophoresis. We have previously characterized the induction of synthesis of 10-16 specific proteins by IFN-alpha 2b in HCs, as analyzed by one-dimensio...
journal_title:Leukemia
pub_type: 杂志文章
doi:
更新日期:1987-04-01 00:00:00
abstract::The immunological bone marrow (BM) microenvironment plays a major role in controlling growth and survival of clonal plasma cells (PC); this might translate into different patterns of expression of molecules involved in immune responses on PC from different types of monoclonal gammopathies (MG). We have studied the exp...
journal_title:Leukemia
pub_type: 杂志文章
doi:10.1038/sj.leu.2403647
更新日期:2005-03-01 00:00:00
abstract::Bruton agammaglobulinemia tyrosine kinase (BTK), a cytoplasmic protein tyrosine kinase, is a component of the B-cell receptor signaling pathway. Ibrutinib, a BTK inhibitor, has demonstrated a significant clinical activity against chronic lymphocytic leukemia (CLL) in early clinical trials. Understanding the molecular ...
journal_title:Leukemia
pub_type: 杂志文章
doi:10.1038/leu.2013.358
更新日期:2014-03-01 00:00:00
abstract::ET is a chronic myeloproliferative disorder rarely evolving into AML, sometimes preceded by a myelodysplastic syndrome (MDS). Such transformations mostly occur in patients treated with radiophosphorous ((32)P) or alkylating agents, especially busulfan. Recently, concern has also arisen about the long-term safety of hy...
journal_title:Leukemia
pub_type: 杂志文章
doi:10.1038/sj.leu.2402638
更新日期:2002-10-01 00:00:00
abstract::Interleukin-4 inhibits several monocyte functions like A23187-induced expression of cytokines and c-fos and c-jun proto-oncogene mRNA expression. In an attempt to elucidate the mechanism by which this inhibitive effect is mediated, we compared the effect of IL-4 on A23187-induced c-fos and c-jun mRNA expression in con...
journal_title:Leukemia
pub_type: 杂志文章
doi:
更新日期:1994-07-01 00:00:00
abstract::After accounting for misdiagnosis and treatment effect, allele-specific (AS)-PCR detects the JAK2V617F mutation in >95% of polycythemia vera (PV) patients. Using database inquiry, we identified 6 of a total 220 cases with PV that were JAK2V617F-negative (prevalence=3%). Of these, five cases ( approximately 80%) were f...
journal_title:Leukemia
pub_type: 杂志文章
doi:10.1038/sj.leu.2404810
更新日期:2007-09-01 00:00:00
abstract::The main reason for the unfavorable clinical outcome of BCR-ABL1-positive acute lymphoblastic leukemia (ALL) is genetic instability. However, how normal B-cell precursors acquire the genetic changes that lead to transformation has not yet been completely defined. We investigated the expression of the activation-induce...
journal_title:Leukemia
pub_type: 杂志文章
doi:10.1038/leu.2009.197
更新日期:2010-01-01 00:00:00
abstract::Trisomy 12 is the most common chromosomal aberration in chronic B lymphocytic leukemia (B-CLL). In this study we have investigated trisomy 12 and posed two major questions: (a) What is the origin of the third copy of chromosome 12? and (b) What is the proportion of trisomy 12 cells in malignant clones with this aberra...
journal_title:Leukemia
pub_type: 杂志文章
doi:
更新日期:1989-12-01 00:00:00
abstract::Immunoglobulin and T cell receptor gene rearrangement and expression were investigated within B cell acute lymphoblastic leukemias (ALLs) that are thought to be representative of the early stages of normal human B cell development. Although the immunoglobulin heavy chain locus is rearranged in leukemic cells from all ...
journal_title:Leukemia
pub_type: 杂志文章
doi:
更新日期:1989-11-01 00:00:00
abstract::The clinical, hematological, and cytogenetic data from two young adults with acute myeloid leukemia (AML) FAB type M1 is described. At diagnosis, cytogenetic investigation revealed the presence of the translocation t(6;9)(p23;q34). Bone marrow basophilia was not detected in either patient nor was there any evidence of...
journal_title:Leukemia
pub_type: 杂志文章,评审
doi:
更新日期:1993-04-01 00:00:00
abstract::Targeted therapies are frequently combined with standard cytotoxic drugs to enhance clinical response. Targeting the B-cell lymphoma 2 (BCL-2) family of proteins is an attractive option to combat chemoresistance in leukemia. Preclinical and clinical studies indicate modest single-agent activity with selective BCL-2 in...
journal_title:Leukemia
pub_type: 杂志文章
doi:10.1038/leu.2017.243
更新日期:2018-02-01 00:00:00
abstract::Myelodysplastic syndromes (MDS) are a group of clonal hematologic disorders found predominantly in the elderly. The molecular mechanisms underlying the development of MDS remain obscure. In order to begin to identify tumor suppressor genes involved in these disorders, we performed a detailed microsatellite allelotype ...
journal_title:Leukemia
pub_type: 杂志文章
doi:10.1038/sj.leu.2401717
更新日期:2000-05-01 00:00:00
abstract::Point mutations within codon 12 of the Harvey (H-) ras proto-oncogene have recently been implicated in the progression of hemopoietic malignancy, particularly chronic myeloid leukemia. We have analyzed DNA from 170 cases of acute and chronic leukemia by using a restriction fragment length polymorphism. No evidence for...
journal_title:Leukemia
pub_type: 杂志文章
doi:
更新日期:1989-01-01 00:00:00
abstract::In 2005, the first guidelines were published on the management of patients with multiple myeloma (MM). An expert panel reviewed the currently available literature as the basis for a set of revised and updated consensus guidelines for the diagnosis and management of patients with MM who are not eligible for autologous ...
journal_title:Leukemia
pub_type: 杂志文章,实务指引,评审
doi:10.1038/leu.2009.122
更新日期:2009-10-01 00:00:00
abstract::Mutations of signal transducing molecules such as Ras have been shown to confer a growth advantage in leukaemic blasts and contribute to the pathogenesis of the disease. Alterations of signal transducing molecules other than Ras may play a role in leukaemogenesis. Knowledge of such mutations could also further our und...
journal_title:Leukemia
pub_type: 杂志文章
doi:
更新日期:1994-09-01 00:00:00
abstract::The Bcr/Abl tyrosine kinase that is expressed from the Philadelphia chromosome protects leukemia cells from apoptosis caused by removal of growth factors or by cytotoxic agents and ionizing irradiation. This resistance to apoptosis is associated with a Bcr/Abl-mediated G2/M delay. Therefore, inhibiting Bcr/Abl signali...
journal_title:Leukemia
pub_type: 杂志文章
doi:10.1038/sj.leu.2401536
更新日期:1999-10-01 00:00:00
abstract::Insulin and insulin growth factor type 1 (IGF-1) and their receptors are closely related molecules, but both factors bind to the receptor of the other one with a weak affinity. No study has presently documented a role of insulin as a myeloma growth factor (MGF) for human multiple myeloma cells (MMCs), whereas many stu...
journal_title:Leukemia
pub_type: 杂志文章
doi:10.1038/leu.2010.192
更新日期:2010-11-01 00:00:00
abstract::The examples discussed above show the profound influence of HIV infection on expression pattern of cell surface proteins and the functional relevance thereof. Altered cell surface pattern is involved in all aspects of HIV-induced pathogenesis such as viral spreading viral adhesion and cellular apoptosis and is an impo...
journal_title:Leukemia
pub_type: 杂志文章,评审
doi:10.1038/sj.leu.2401322
更新日期:1999-04-01 00:00:00
abstract::Myeloid growth factors, such as granulocyte colony-stimulating factor and granulocyte-macrophage colony-stimulating factor, have been used to decrease the duration of chemotherapy-induced neutropenia and thereby reduce the incidence and severity of infections in various regimens used to treat acute myeloid leukemia an...
journal_title:Leukemia
pub_type: 杂志文章,评审
doi:10.1038/sj.leu.2404152
更新日期:2006-04-01 00:00:00
abstract::Cell lines of myeloid origin have been shown to express interleukin-2 receptors (IL-2R). Here, we demonstrate the expression of IL-2R alpha and IL-R beta on the CML blast cell line K562 by FACS analysis and cross-linking assay. Furthermore, we examined the effect of IL-2 on leukemic progenitor growth, employing K562 a...
journal_title:Leukemia
pub_type: 杂志文章
doi:
更新日期:1995-03-01 00:00:00
abstract::In all, 17 consecutive patients in hematological complete remission (HCR) of acute promyelocytic leukemia (APL) received allogeneic stem cell transplantation (SCT) from an HLA-identical sibling and were monitored by reverse transcriptase polymerase chain reaction of PML/RARalpha prior and after transplant. Median age ...
journal_title:Leukemia
pub_type: 杂志文章
doi:10.1038/sj.leu.2403078
更新日期:2003-10-01 00:00:00
abstract::Molecular cloning of immunoglobulin heavy chain (IGH) translocation breakpoints identifies genes of biological importance in the development of normal and malignant B cells. Long-distance inverse PCR (LDI-PCR) was first applied to amplification of IGH gene translocations targeted to the joining (IGHJ) regions. We repo...
journal_title:Leukemia
pub_type: 杂志文章
doi:10.1038/sj.leu.2403500
更新日期:2004-12-01 00:00:00
abstract::PRDM1/BLIMP-1, a master regulator of plasma-cell differentiation, is frequently inactivated in activated B-cell-like (ABC) diffuse large B-cell lymphoma (DLBCL) patients. Little is known about its genetic aberrations and relevant clinical implications. A large series of patients with de novo DLBCL was effectively eval...
journal_title:Leukemia
pub_type: 杂志文章
doi:10.1038/leu.2016.243
更新日期:2017-03-01 00:00:00
abstract::The t(9;11)(p21;q23) has been associated with characteristic clinical features and a superior treatment outcome in previously untreated pediatric acute myeloblastic leukemia (AML), but has not been well studied in children with secondary AML. This translocation was detected in 6.7% of de novo and 46% of secondary AML ...
journal_title:Leukemia
pub_type: 杂志文章
doi:
更新日期:1992-06-01 00:00:00
abstract::Because of their substantial in vitro synergy, we conducted a dose-escalation study of cyclophosphamide (CP) added to 2-chloro-2'-deoxyadenosine (CdA) in patients with previously treated chronic lymphocytic leukemia and non-Hodgkin's lymphoma. CdA was given at a fixed dose (5.6 mg/m2/day) as a 2-h intravenous (i.v.) i...
journal_title:Leukemia
pub_type: 临床试验,杂志文章
doi:10.1038/sj.leu.2401783
更新日期:2000-06-01 00:00:00
abstract::Chromosomal translocations involving the MYC oncogene are a hallmark of Burkitt lymphoma but they are only found in a varying frequency in mature Burkitt-type acute lymphoblastic leukemia (B-ALL). We have investigated samples of 56 sporadic Burkitt leukemia/lymphoma patients for the translocations t(8;14)(q24;q32), t(...
journal_title:Leukemia
pub_type: 杂志文章
doi:10.1038/sj.leu.2403847
更新日期:2005-08-01 00:00:00
abstract::Current MRD studies in T-cell acute lymphoblastic leukemia (T-ALL) mainly use T-cell receptor gamma, delta and SIL-TAL1 gene rearrangements as MRD-PCR targets. However, low frequency or limited diversity of these markers restricts the number of evaluable patients, particularly because two markers are recommended for M...
journal_title:Leukemia
pub_type: 杂志文章
doi:10.1038/sj.leu.2403263
更新日期:2004-04-01 00:00:00