Immunoglobulin genes in multiple myeloma: expressed and non-expressed repertoires, heavy and light chain pairings and somatic mutation patterns in a series of 101 cases.

Abstract:

BACKGROUND AND OBJECTIVES:The available data on the immunoglobulin gene (IG) repertoire in multiple myeloma (MM) derive mainly from heavy chains; considerably less is known about light chains. We assessed in parallel IGH and IGK/IGL rearrangements in 101 MM patients so as to gain insight into: (i) IG repertoires; (ii) antigen impact; (iii) the role of receptor editing. DESIGN AND METHODS:Bone marrow aspirates were collected from all cases. IGHV-(D)-J and IGLV-J rearrangements were amplified by reverse transcriptase polymerase chain reaction (PCR). In all cases, IGKV-J rearrangements were analyzed in parallel on cDNA/genomic DNA. IGKV-KDE and IGKJ-C-INTRON-KDE were also amplified by DNA-PCR. RT-PCR products were directly sequenced. RESULTS:IGHV3 genes predominated; the IGHV4-34 gene was used in only one case. Five IGKV and five IGLV genes accounted for the majority of in-frame, transcribed IGKV-J or IGLV-J rearrangements. Taking IGKV-J, IGKV-KDE and IGKJ-C-INTRON-KDE rearrangements together, biallelic IGK locus rearrangements were detected in 22/43 k-MM cases. In l-MM, 36/42 cases had at least one rearranged IGK allele; 8/19 IGKV-J rearrangements in l-MM were in-frame. All in-frame, transcribed IGH/IGK/IGL sequences were mutated; parallel heavy/light chain analysis demonstrated a comparable impact of somatic hypermutation. INTERPRETATION AND CONCLUSIONS:Biases in IG repertoire did not seem disease-related but followed a similar pattern to that of the normal repertoire. The under-representation of the IGHV4-34 gene provides an explanation for the paucity of autoimmune phenomena in MM. Somatic mutation patterns indicate the complementary role of MM IGH/IGK/IGL sequences in antigen recognition. Finally, the frequent inactivation of productive IGKV-J joints by secondary rearrangements in MM suggests active receptor editing.

journal_name

Haematologica

journal_title

Haematologica

authors

Hadzidimitriou A,Stamatopoulos K,Belessi C,Lalayianni C,Stavroyianni N,Smilevska T,Hatzi K,Laoutaris N,Anagnostopoulos A,Kollia P,Fassas A

subject

Has Abstract

pub_date

2006-06-01 00:00:00

pages

781-7

issue

6

eissn

0390-6078

issn

1592-8721

journal_volume

91

pub_type

杂志文章
  • Resolution of bone marrow fibrosis in a patient receiving JAK1/JAK2 inhibitor treatment with ruxolitinib.

    abstract:UNLABELLED:Ruxolitinib, a JAK1/JAK2 inhibitor, is currently the only pharmacological agent approved for the treatment of myelofibrosis. Approval was based on findings from two phase 3 trials comparing ruxolitinib with placebo (COMFORT-I) and with best available therapy (COMFORT-II) for the treatment of primary or secon...

    journal_title:Haematologica

    pub_type: 杂志文章,多中心研究,随机对照试验

    doi:10.3324/haematol.2013.095109

    authors: Wilkins BS,Radia D,Woodley C,Farhi SE,Keohane C,Harrison CN

    更新日期:2013-12-01 00:00:00

  • Concomitant aberrant overexpression of RUNX1 and NCAM in regenerating bone marrow of myeloid leukemia of Down's syndrome.

    abstract:BACKGROUND AND OBJECTIVES:Myeloid leukemia of Down's syndrome (ML-DS) has characteristic biological features (e.g. expression of the truncated GATA1s), which are different from those of non-DS childhood acute myeloid leukemias (AML). The objective of this study was to investigate factors predisposing to the development...

    journal_title:Haematologica

    pub_type: 杂志文章

    doi:

    authors: Langebrake C,Klusmann JH,Wortmann K,Kolar M,Puhlmann U,Reinhardt D

    更新日期:2006-11-01 00:00:00

  • Translocation t(9;14)(p13;q32) in cases of splenic marginal zone lymphoma.

    abstract::Translocation t(9;14)(p13;q32) involving PAX5 and IGH genes was first described in lymphoplasmacytic lymphoma. New data suggest that this translocation is not restricted to a specific morphologic subtype but occurs in other B-cell lymphomas. We present three cases with a diagnosis of splenic marginal zone lymphoma and...

    journal_title:Haematologica

    pub_type: 信件

    doi:

    authors: Baró C,Salido M,Domingo A,Granada I,Colomo L,Serrano S,Solé F

    更新日期:2006-09-01 00:00:00

  • Eosinophils and C4 predict clinical failure of combination immunotherapy with very low dose subcutaneous interleukin-2 and interferon in renal cell carcinoma patients.

    abstract:BACKGROUND AND OBJECTIVE:The clinical and immunologic activities of interleukin-2 (IL-2) in cancer patients have been extensively studied and described; however, in most of these studies, IL-2 was administered by intravenous bolus or continuous infusion, while the immunologic effects of IL-2 given by the subcutaneous (...

    journal_title:Haematologica

    pub_type: 杂志文章

    doi:

    authors: Moroni M,Porta C,De Amici M,Quaglini S,Cattabiani MA,Buzio C

    更新日期:2000-03-01 00:00:00

  • CD36 defines primitive chronic myeloid leukemia cells less responsive to imatinib but vulnerable to antibody-based therapeutic targeting.

    abstract::Tyrosine kinase inhibitors (TKIs) are highly effective for the treatment of chronic myeloid leukemia (CML), but very few patients are cured. The major drawbacks regarding TKIs are their low efficacy in eradicating the leukemic stem cells responsible for disease maintenance and relapse upon drug cessation. Herein, we p...

    journal_title:Haematologica

    pub_type: 杂志文章

    doi:10.3324/haematol.2017.169946

    authors: Landberg N,von Palffy S,Askmyr M,Lilljebjörn H,Sandén C,Rissler M,Mustjoki S,Hjorth-Hansen H,Richter J,Ågerstam H,Järås M,Fioretos T

    更新日期:2018-03-01 00:00:00

  • Autoimmunity and the risk of myeloproliferative neoplasms.

    abstract::The causes of myeloproliferative neoplasm (MPN) are unknown. We conducted a large population-based study including 11,039 myeloproliferative neoplasm patients and 43,550 matched controls with the aim of assessing the associations between a personal history of a broad span of autoimmune diseases and subsequent risk of ...

    journal_title:Haematologica

    pub_type: 杂志文章

    doi:10.3324/haematol.2009.020412

    authors: Kristinsson SY,Landgren O,Samuelsson J,Björkholm M,Goldin LR

    更新日期:2010-07-01 00:00:00

  • Pediatric acute lymphoblastic leukemia.

    abstract::The last decade has witnessed great advances in our understanding of the genetic and biological basis of childhood acute lymphoblastic leukemia (ALL), the development of experimental models to probe mechanisms and evaluate new therapies, and the development of more efficacious treatment stratification. Genomic analyse...

    journal_title:Haematologica

    pub_type: 杂志文章

    doi:10.3324/haematol.2020.247031

    authors: Inaba H,Mullighan CG

    更新日期:2020-11-01 00:00:00

  • Unusual clonal evolution involving 5q in a case of myelodysplastic syndrome with deletion 5q 31 treated with lenalidomide.

    abstract::Lenalidomide is a very active drug in myelodysplastic syndrome with del (5q). We report such a patient treated with this drug who developed unusual complex cytogenetic abnormalities, which were elucidated by multi-FISH and FISH analysis as jumping translocations involving the long arm of chromosome 5, that resulted in...

    journal_title:Haematologica

    pub_type: 信件

    doi:10.3324/haematol.11917

    authors: Eclache V,Da Rocha A,Le Roux G,Fenaux P

    更新日期:2008-02-01 00:00:00

  • Interferon-alpha 2b is not effective in the treatment of refractory immune thrombocytopenic purpura.

    abstract::About 25-30% of patients with immune thrombocytopenic purpura (ITP) are refractory to corticosteroids, splenectomy and other treatments. It has been suggested that interferon-alpha 2b (IFN-alpha 2b) may be useful in the treatment of chronic refractory ITP patients. We treated 9 chronic refractory ITP patients with IFN...

    journal_title:Haematologica

    pub_type: 信件

    doi:

    authors: Vianelli N,Tazzari PL,Baravelli S,Ricci F,Valdrè L,Tura S

    更新日期:1998-08-01 00:00:00

  • The long-term impact of in vitro drug sensitivity on risk stratification and treatment outcome in acute lymphoblastic leukemia of childhood (CoALL 06-97).

    abstract:BACKGROUND:In a study of childhood acute lymphoblastic leukemia (CoALL 06-97 study), the in vitro sensitivity of the patients' cells to prednisolone, vincristine and asparaginase was introduced as a new additional risk parameter for treatment stratification. In parallel in vivo treatment response was assessed by determ...

    journal_title:Haematologica

    pub_type: 杂志文章

    doi:10.3324/haematol.2010.039735

    authors: Escherich G,Tröger A,Göbel U,Graubner U,Pekrun A,Jorch N,Kaspers G,Zimmermann M,zur Stadt U,Kazemier K,Pieters R,Den Boer ML,Horstmann M,Janka GE,CoALL study group, Hamburg, Germany.

    更新日期:2011-06-01 00:00:00

  • Immunosuppressive therapy with anti-thymocyte globulin and cyclosporine A in selected children with hypoplastic refractory cytopenia.

    abstract::It is currently unknown whether immunosuppressive therapy or hematopoietic stem cell transplantation is the most appropriate treatment strategy for children with refractory cytopenia and normal karyotype or trisomy 8. We report on 31 children with hypoplastic refractory cytopenia treated with immunosuppressive therapy...

    journal_title:Haematologica

    pub_type: 杂志文章

    doi:10.3324/haematol.10683

    authors: Yoshimi A,Baumann I,Führer M,Bergsträsser E,Göbel U,Sykora KW,Klingebiel T,Gross-Wieltsch U,van den Heuvel-Eibrink MM,Fischer A,Nöllke P,Niemeyer C

    更新日期:2007-03-01 00:00:00

  • Increased plasma thrombopoietin levels in patients with myelodysplastic syndrome: a reliable marker for a benign subset of bone marrow failure.

    abstract::Although myelodysplastic syndromes are heterogeneous disorders comprising a benign subset of bone marrow failure similar to aplastic anemia, no laboratory test has been established to distinguish it from bone marrow failures that can evolve into acute myeloid leukemia. Plasma thrombopoietin levels were measured in 120...

    journal_title:Haematologica

    pub_type: 杂志文章

    doi:10.3324/haematol.2012.066217

    authors: Seiki Y,Sasaki Y,Hosokawa K,Saito C,Sugimori N,Yamazaki H,Takami A,Nakao S

    更新日期:2013-06-01 00:00:00

  • Targeting CD47/TNFAIP8 by miR-155 overcomes drug resistance and inhibits tumor growth through induction of phagocytosis and apoptosis in multiple myeloma.

    abstract::The mechanisms of drug resistance in multiple myeloma are poorly understood. Here we show that CD47, an integrin-associated receptor, is significantly upregulated in drug resistant myeloma cells in comparison with parental cells, and that high expression of CD47 detected by immunohistochemistry is associated with shor...

    journal_title:Haematologica

    pub_type: 杂志文章

    doi:10.3324/haematol.2019.227579

    authors: Rastgoo N,Wu J,Liu A,Pourabdollah M,Atenafu EG,Reece D,Chen W,Chang H

    更新日期:2020-12-01 00:00:00

  • Effect of hematologic response on outcome of patients undergoing transplantation for primary amyloidosis: importance of achieving a complete response.

    abstract::Our objective was to determine whether the goal of high-dose therapy should be a partial hematologic response or a complete response. We analyzed 282 consecutive stem cell transplant patients. A partial hematologic response was achieved in 108 patients (38%), and 93 (33%) achieved a complete hematologic response. Surv...

    journal_title:Haematologica

    pub_type: 杂志文章

    doi:10.3324/haematol.11413

    authors: Gertz MA,Lacy MQ,Dispenzieri A,Hayman SR,Kumar SK,Leung N,Gastineau DA

    更新日期:2007-10-01 00:00:00

  • Beta-, delta beta-thalassemia and Hb lepore among Yugoslav, Bulgarian, Turkish and Albanian.

    abstract::Over the past 20 years we have studied 1781 patients with beta-thalassemia syndromes of which 1481 Yugoslav, 166 Bulgarian, 102 Turkish and 32 Albanian. In this paper we summarize the data on the heterogeneity and molecular basis of beta-thal, delta beta-thal and Lepore hemoglobinopathy in these four nationalities liv...

    journal_title:Haematologica

    pub_type: 杂志文章

    doi:

    authors: Efremov GD

    更新日期:1990-09-01 00:00:00

  • Diagnosis of platelet-type von Willebrand disease by flow cytometry.

    abstract::Platelet-type von Willebrand disease (PT-VWD) is a rare autosomal dominant bleeding disorder which is due to a mutation in the gene encoding for platelet glycoprotein Ibalpha (GPIbalpha) resulting in enhanced affinity for von Willebrand factor (VWF). PT-VWD is often mistakenly diagnosed as type 2B VWD for the similari...

    journal_title:Haematologica

    pub_type: 杂志文章

    doi:10.3324/haematol.2009.015990

    authors: Giannini S,Cecchetti L,Mezzasoma AM,Gresele P

    更新日期:2010-06-01 00:00:00

  • Outcomes after late bone marrow and very early central nervous system relapse of childhood B-acute lymphoblastic leukemia: a report from the Children's Oncology Group phase III study AALL0433.

    abstract::Outcomes after relapse of childhood B-acute lymphoblastic leukemia (B-ALL) are poor, and optimal therapy is unclear. Children's Oncology Group study AALL0433 evaluated a new platform for relapsed ALL. Between March 2007 and October 2013 AALL0433 enrolled 275 participants with late bone marrow or very early isolated ce...

    journal_title:Haematologica

    pub_type: 杂志文章

    doi:10.3324/haematol.2019.237230

    authors: Lew G,Chen Y,Lu X,Rheingold SR,Whitlock JA,Devidas M,Hastings CA,Winick NJ,Carroll WL,Wood BL,Borowitz MJ,Pulsipher MA,Hunger SP

    更新日期:2021-01-01 00:00:00

  • Once-weekly versus twice-weekly carfilzomib in patients with newly diagnosed multiple myeloma: a pooled analysis of two phase I/II studies.

    abstract::Twice-weekly carfilzomib is approved at 27 and 56 mg/m2 to treat relapsed multiple myeloma patients. In the phase III study ARROW, once-weekly 70 mg/m 2 carfilzomib prolonged the median progression-free survival of relapsed multiple myeloma patients in comparison with twice-weekly 27 mg/m2 carfilzomib, without adding ...

    journal_title:Haematologica

    pub_type: 杂志文章

    doi:10.3324/haematol.2018.208272

    authors: Bringhen S,Mina R,Petrucci MT,Gaidano G,Ballanti S,Musto P,Offidani M,Spada S,Benevolo G,Ponticelli E,Galieni P,Cavo M,Di Toritto TC,Di Raimondo F,Montefusco V,Palumbo A,Boccadoro M,Larocca A

    更新日期:2019-08-01 00:00:00

  • Impaired killing of Candida albicans by granulocytes mobilized for transfusion purposes: a role for granule components.

    abstract::Granulocyte transfusions are used to treat neutropenic patients with life-threatening bacterial or fungal infections that do not respond to anti-microbial drugs. Donor neutrophils that have been mobilized with granulocyte-colony stimulating factor (G-CSF) and dexamethasone are functional in terms of antibacterial acti...

    journal_title:Haematologica

    pub_type: 杂志文章

    doi:10.3324/haematol.2015.136630

    authors: Gazendam RP,van de Geer A,van Hamme JL,Tool AT,van Rees DJ,Aarts CE,van den Biggelaar M,van Alphen F,Verkuijlen P,Meijer AB,Janssen H,Roos D,van den Berg TK,Kuijpers TW

    更新日期:2016-05-01 00:00:00

  • European Myeloma Network recommendations on the evaluation and treatment of newly diagnosed patients with multiple myeloma.

    abstract::Multiple myeloma management has undergone profound changes in the past thanks to advances in our understanding of the disease biology and improvements in treatment and supportive care approaches. This article presents recommendations of the European Myeloma Network for newly diagnosed patients based on the GRADE syste...

    journal_title:Haematologica

    pub_type: 杂志文章,实务指引

    doi:10.3324/haematol.2013.099358

    authors: Engelhardt M,Terpos E,Kleber M,Gay F,Wäsch R,Morgan G,Cavo M,van de Donk N,Beilhack A,Bruno B,Johnsen HE,Hajek R,Driessen C,Ludwig H,Beksac M,Boccadoro M,Straka C,Brighen S,Gramatzki M,Larocca A,Lokhorst H,Magar

    更新日期:2014-02-01 00:00:00

  • Autoimmune hemolytic anemia in multicentric Castleman's disease.

    abstract::We report on a patient affected by multicentric Castleman's disease who developed an acute immunohemolytic anemia due to warm antibody. The clinical course was characterized by refractoriness to the steroidal treatment and by a dramatic improvement of the hematological and objective picture following combination chemo...

    journal_title:Haematologica

    pub_type: 杂志文章

    doi:

    authors: Liberato NL,Bollati P,Chiofalo F,Filipponi M,Poli M

    更新日期:1996-01-01 00:00:00

  • Heterogeneous breakpoints in patients with acute lymphoblastic leukemia and the dic(9;20)(p11-13;q11) show recurrent involvement of genes at 20q11.21.

    abstract::The dic(9;20)(p11-13;q11) is a recurrent chromosomal abnormality in patients with acute lymphoblastic leukemia. Although it results in loss of material from 9p and 20q, the molecular targets on both chromosomes have not been fully elucidated. From an initial cohort of 58 with acute lymphoblastic leukemia patients with...

    journal_title:Haematologica

    pub_type: 杂志文章

    doi:10.3324/haematol.2008.002808

    authors: An Q,Wright SL,Moorman AV,Parker H,Griffiths M,Ross FM,Davies T,Harrison CJ,Strefford JC

    更新日期:2009-08-01 00:00:00

  • Immune reconstitution after autologous hematopoietic stem cell transplantation in relation to underlying disease, type of high-dose therapy and infectious complications.

    abstract:BACKGROUND AND OBJECTIVES:Autologous peripheral stem cell transplantation (APSCT) is increasingly used for various hematologic malignancies and solid tumors. The objective of this study was to analyze the immune reconstitution after APSCT and see if there was any correlation with diagnosis, age, type of high-dose thera...

    journal_title:Haematologica

    pub_type: 杂志文章

    doi:

    authors: Steingrimsdottir H,Gruber A,Björkholm M,Svensson A,Hansson M

    更新日期:2000-08-01 00:00:00

  • Hemoglobin sickle cell disease complications: a clinical study of 179 cases.

    abstract:BACKGROUND:Hemoglobin sickle cell disease is one of the most frequent hemoglobinopathies. Surprisingly, few studies have been dedicated to this disease, currently considered to be a mild variant of homozygous sickle cell disease. The aim of this study was to update our knowledge about hemoglobin sickle cell disease. D...

    journal_title:Haematologica

    pub_type: 杂志文章

    doi:10.3324/haematol.2011.055202

    authors: Lionnet F,Hammoudi N,Stojanovic KS,Avellino V,Grateau G,Girot R,Haymann JP

    更新日期:2012-08-01 00:00:00

  • Optimizing peripheral blood progenitor cell autologous transplantation in multiple myeloma.

    abstract::As in other malignancies, peripheral blood progenitor cells (PBPC) have almost completely replaced bone marrow as the source of stem cells for autologous transplantation in multiple myeloma. PBPC collection could be optimized either by reducing contamination by the malignant clone or by increasing hematopoietic qualit...

    journal_title:Haematologica

    pub_type: 临床试验,杂志文章,随机对照试验,评审

    doi:

    authors: Harousseau JL

    更新日期:1999-06-01 00:00:00

  • Minor histocompatibility antigen HA-8 mismatch and clinical outcome after HLA-identical sibling donor allogeneic stem cell transplantation.

    abstract::We analyzed the clinical outcome of 146 adult patients receiving an HLA-identical sibling donor stem cell transplant depending on HA-8 matching status. The presence of an HA-8 mismatch was associated with an increased risk of severe acute graft-versus-host disease and with a worse overall survival. ...

    journal_title:Haematologica

    pub_type: 信件

    doi:

    authors: Pérez-García A,De la Cámara R,Torres A,González M,Jiménez A,Gallardo D

    更新日期:2005-12-01 00:00:00

  • Effect of interleukin-1beta and glutathione S-transferase genotypes on the development of gastric mucosa-associated lymphoid tissue lymphoma.

    abstract::e tested whether polymorphic variations in glutathione S-transferase genes (GSTM1, GSTT1, GSTP1) and interleukin-1 (IL-1beta and IL-1RN) genes confer susceptibility to mucosa-associated lymphoid tissue lymphomas (MALT) in a Chinese population. The rates of GSTM1, GSTP1, IL-1beta and IL-1RN genotypes did not differ bet...

    journal_title:Haematologica

    pub_type: 信件

    doi:

    authors: Wu MS,Shun CT,Huang SP,Cheng AL,Chen LT,Lin JT

    更新日期:2004-08-01 00:00:00

  • Identification of a novel PROS1 c.1113T-->GG frameshift mutation in a family with mixed type I/type III protein S deficiency.

    abstract::We report a family with type I and type III protein S (PS) deficiency, which showed to be phenotypic variants of the same genetic disease. Direct sequencing analysis of the PROS1 gene was performed to establish the genotype. The ratio of protein C antigen and total PS antigen levels (protein C/S ratio) was used to cla...

    journal_title:Haematologica

    pub_type: 信件

    doi:

    authors: ten Kate MK,Mulder R,Platteel M,Brouwer JL,van der Steege G,van der Meer J

    更新日期:2006-08-01 00:00:00

  • Effectiveness of subcutaneous low-dose alemtuzumab and rituximab combination therapy for steroid-resistant chronic graft-versus-host disease.

    abstract:BACKGROUND:Chronic graft-versus-host disease is a common late complication of allogeneic hematopoietic stem cell transplantation. Corticosteroids are the standard initial treatment. Second-line treatment has not been well defined. We evaluated the effectiveness and safety of low doses of alemtuzumab plus low doses of r...

    journal_title:Haematologica

    pub_type: 杂志文章

    doi:10.3324/haematol.2011.054577

    authors: Gutiérrez-Aguirre CH,Cantú-Rodríguez OG,Borjas-Almaguer OD,González-Llano O,Jaime-Pérez JC,Solano-Genesta M,Gómez-Guijosa M,Mancias-Guerra C,Tarin L,Gómez-Almaguer D

    更新日期:2012-05-01 00:00:00

  • Monoclonal expansion of large granular lymphocytes with a CD4+ CD8dim+/- phenotype associated with hairy cell leukemia.

    abstract::Peripheral blood lymphoid cell expansions with an unusual CD3+, CD4+, CD8dim+/-, CD11b+, CD57+ immunophenotype have recently been reported. They frequently have the morphology of large granular lymphocytes (LGL) and can be either monoclonal or polyclonal. Their significance is still unclear and no association with hem...

    journal_title:Haematologica

    pub_type: 杂志文章

    doi:

    authors: Airò P,Rossi G,Facchetti F,Marocolo D,Garza L,Lanfranchi A,Prati E,Brugnoni D,Malacarne F,Cattaneo R

    更新日期:1995-03-01 00:00:00