Perspectives on familial chronic lymphocytic leukemia: genes and the environment.


:Chronic lymphocytic leukemia (CLL) comprises a substantial proportion of leukemias in adults in the western hemisphere. Male gender, increasing age, ethnicity (high in Caucasians, lowest in Asians), and family history are risk factors. Although no specific extrinsic etiologic factors have been established, farming and pesticide exposure are associated with increased risk. Migration studies confirm that ethnic groups retain the risk associated with their origin rather than their new location, favoring a role for heredity. Kindreds with multiple cases of CLL have been well described in the literature and studies in large populations confirm that lymphoproliferative malignancies and especially CLL occur together at a rate that cannot be attributed to chance. Since environmental factors cannot readily explain the familial aggregations, a hereditary factor that affects susceptibility to CLL is likely. The identification of clones that are immunophenotypically identical to CLL in healthy individuals from CLL kindreds (14% to 18%) as well as in the general population (3.5% in age bracket >65 years) suggests a possible precursor condition, but longitudinal studies will be necessary to establish significance in the general population. Family (linkage) and population (candidate gene) studies to date have been too small to identify the specific genes that account for increased susceptibility; larger studies including planned consortia to identify additional high-risk kindreds for genetic studies, as well as the application of advanced technologies such as genomics, cytogenetic, expression, and proteomics, are widely expected to advance understanding over the next few years.


Semin Hematol


Seminars in hematology


Caporaso N,Marti GE,Goldin L




Has Abstract


2004-07-01 00:00:00














  • Impact of social media for the hematologist/oncologist.

    abstract::In the era of modern communication, the physician and patient relationship has evolved to include an entirely new dimension-social media. This new dimension offers several opportunities for patient education, research and its dissemination, and professional development for health care providers; it can also serve as a...

    journal_title:Seminars in hematology

    pub_type: 杂志文章,评审


    authors: Abuhadra N,Majhail NS,Nazha A

    更新日期:2017-10-01 00:00:00

  • TET-dioxygenase deficiency in oncogenesis and its targeting for tumor-selective therapeutics.

    abstract::TET2 is one of the most frequently mutated genes in myeloid neoplasms. TET2 loss-of-function perturbs myeloid differentiation and causes clonal expansion. Despite extensive knowledge regarding biochemical mechanisms underlying distorted myeloid differentiation, targeted therapies are lagging. Here we review known bioc...

    journal_title:Seminars in hematology

    pub_type: 杂志文章


    authors: Guan Y,Hasipek M,Tiwari AD,Maciejewski JP,Jha BK

    更新日期:2021-01-01 00:00:00

  • Familial thrombophilia: a complex genetic disorder.

    abstract::Familial thrombosis has long been considered as an autosomal dominant trait, caused by a dominant gene defect with a reduced penetrance for the disease. Recently, this view has changed and today familial thrombophilia is considered as a complex genetic disorder caused by the segregation of two or more gene defects (kn...

    journal_title:Seminars in hematology

    pub_type: 杂志文章,评审


    authors: Koeleman BP,Reitsma PH,Bertina RM

    更新日期:1997-07-01 00:00:00

  • Apoptosis and cancer: strategies for integrating programmed cell death.

    abstract::Virtually all human cells are endowed with the capacity to commit suicide using an evolutionarily conserved mechanism that involves activation of caspase-family cell death proteases. Caspase activation culminates in a cell death process known as "apoptosis." The activation of these intracellular proteases is carefully...

    journal_title:Seminars in hematology

    pub_type: 杂志文章,评审


    authors: Reed CJ

    更新日期:2000-10-01 00:00:00

  • Idiopathic thrombocytopenia purpura: Treatment patterns and an analysis of cost associated with intravenous immunoglobulin and anti-D therapy.

    abstract::A retrospective study was conducted to determine treatment patterns for idiopathic thrombocytopenia purpura (ITP) across the US and to determine the cost of its treatment with high-dose intravenous immunoglobulin (IVIg) and anti-D therapy. Information on the incidence, treatment patterns, hospital care, and costs for ...

    journal_title:Seminars in hematology

    pub_type: 杂志文章


    authors: Simpson KN,Coughlin CM,Eron J,Bussel JB

    更新日期:1998-01-01 00:00:00

  • Predictive genetic variants for venous thrombosis: what's new?

    abstract::Various pathways lead to the development of venous thrombosis. Risk factors are common and can be genetic or acquired. Since the identification of factor V Leiden and prothrombin 20210 G-->A, the field of genetic epidemiology has developed rapidly and many new genetic variants have been described in the past decade. H...

    journal_title:Seminars in hematology

    pub_type: 杂志文章,评审


    authors: Bezemer ID,Rosendaal FR

    更新日期:2007-04-01 00:00:00

  • Catheter coatings, blood flow, and biocompatibility.

    abstract::Thrombus forms on catheters and other indwelling synthetic materials. Systemic heparin infusion decreases, but does not eliminate thrombus formation. The day is approaching when systemic heparinization may no longer be indicated to suppress catheter thrombogenesis. Passivation of catheters by heparin immobilization is...

    journal_title:Seminars in hematology

    pub_type: 杂志文章,评审


    authors: Eberhart RC,Clagett CP

    更新日期:1991-10-01 00:00:00

  • Monitoring inhibitor patients with the right assays.

    abstract::The inhibitor titer is the most important clinical measurement in inhibitor patients, and the Nijmegen method is preferable to the original and well-established Bethesda assay for this purpose; however, both methods have high inter-laboratory variability. Monitoring inhibitor patients after treatment with bypassing ag...

    journal_title:Seminars in hematology

    pub_type: 杂志文章,评审


    authors: Barrowcliffe TW

    更新日期:2008-04-01 00:00:00

  • Survival signals in leukemic large granular lymphocytes.

    abstract::The central hypothesis of our laboratory research program in large granular lymphocyte (LGL) leukemia is that leukemic LGL represent antigen-driven cytotoxic T lymphocytes (CTL) with characteristics of dysregulated apoptosis. The clinical features of LGL leukemia highlight the association of autoimmune diseases such a...

    journal_title:Seminars in hematology

    pub_type: 杂志文章,评审


    authors: Epling-Burnette PK,Loughran TP Jr

    更新日期:2003-07-01 00:00:00

  • Antibody-targeted therapy for myeloid leukemia.

    abstract::The availability of antibodies reactive with antigens expressed only by hematopoietic cells has provided clinical investigators with new tools for use in developing therapies for acute myeloid leukemia (AML). Studies performed to date have investigated the use of such antibodies in an unmodified state, combined with p...

    journal_title:Seminars in hematology

    pub_type: 杂志文章,评审


    authors: Appelbaum FR

    更新日期:1999-10-01 00:00:00

  • Relapsed/Refractory multiple myeloma: defining refractory disease and identifying strategies to overcome resistance.

    abstract::Despite the development of more effective therapies for multiple myeloma (MM) over the past decade, nearly all patients will eventually experience disease relapse and require further therapy. Designing the next generation of therapies for relapsed and refractory disease will depend on understanding the complex molecul...

    journal_title:Seminars in hematology

    pub_type: 杂志文章


    authors: Siegel DS

    更新日期:2012-07-01 00:00:00

  • Novel agents in the treatment of Hodgkin lymphoma: Biological basis and clinical results.

    abstract::Hodgkin Lymphoma (HL) is a lymphoproliferative disorder of B cells that commonly has a favorable prognosis when treated with either combination chemotherapy and radiation therapy, or chemotherapy alone. However, the prognosis for patients who relapse, or have evidence for refractory disease, is poor and new treatments...

    journal_title:Seminars in hematology

    pub_type: 杂志文章,评审


    authors: Younes A,Ansell SM

    更新日期:2016-07-01 00:00:00

  • Somatic Mutations in Philadelphia Chromosome-Negative Myeloproliferative Neoplasms.

    abstract::Myeloproliferative neoplasms (MPN) include polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF). MPN are characterized by clonal proliferation of myeloid progenitors leading to erythrocytosis, thrombocytosis, or leukocytosis, and risk of hemorrhagic and thrombotic events, as well as ...

    journal_title:Seminars in hematology

    pub_type: 杂志文章,评审


    authors: Ferreira Cristina S,Polo B,Lacerda JF

    更新日期:2018-10-01 00:00:00

  • Nonablative stem cell transplantation for older patients with acute leukemias and myelodysplastic syndromes.

    abstract::High-dose chemoradiotherapy with allogeneic bone marrow or peripheral blood stem cell transplantation (SCT) is a potentially curative treatment for advanced or poor-prognosis hematological malignancies. This procedure was initially considered as a means to deliver supralethal doses of chemotherapy and radiation for th...

    journal_title:Seminars in hematology

    pub_type: 杂志文章,评审


    authors: Giralt S,Anagnostopoulos A,Shahjahan M,Champlin R

    更新日期:2002-01-01 00:00:00

  • ZAP-70 and defects of T-cell receptor signaling.

    abstract::The activation, function, and development of peripheral T lymphocytes are dependent on the ability to signal properly through the surface T-cell antigen receptor (TCR)-CD3 complex. Transmission of such signals requires the activation of specific cytoplasmic protein tyrosine kinases (PTK) associated with the TCR. Recen...

    journal_title:Seminars in hematology

    pub_type: 杂志文章,评审


    authors: Elder ME

    更新日期:1998-10-01 00:00:00

  • NK cells as adoptive cellular therapy for hematological malignancies: Advantages and hurdles.

    abstract::Natural killer cells are an essential component of the innate immune system and play a crucial role in immunity against malignancies, without, at difference with T cells, requiring antigen priming or inducing graft-versus-host-disease. Hence, Natural Killer cells can provide a valuable source of allogeneic "off-the-sh...

    journal_title:Seminars in hematology

    pub_type: 杂志文章


    authors: Caruso S,De Angelis B,Carlomagno S,Del Bufalo F,Sivori S,Locatelli F,Quintarelli C

    更新日期:2020-10-01 00:00:00

  • Congenital Defects in the Expression of the Glycosylphosphatidylinositol-Anchored Complement Regulatory Proteins CD59 and Decay-Accelerating Factor.

    abstract::CD59 and decay-accelerating factor (DAF) are glycosylphosphatidylinositol (GPI)-anchored complement regulatory proteins critical for regulating complement activation on the host cell surface. Defective expressions of CD59 or DAF caused by mutations in the genes coding for these proteins or genes involved in the biosyn...

    journal_title:Seminars in hematology

    pub_type: 杂志文章,评审


    authors: Kinoshita T

    更新日期:2018-07-01 00:00:00

  • Experience of the Polycythemia Vera Study Group with essential thrombocythemia: a final report on diagnostic criteria, survival, and leukemic transition by treatment.

    abstract::This report suggests modest changes in the criteria used for the diagnosis of ET and allows tentative recommendations concerning therapy. As outlined in Table I, we believe that absent stainable marrow iron does not necessarily indicate iron deficiency in these patients and that the serum ferritin and RBC mean corpusc...

    journal_title:Seminars in hematology

    pub_type: 杂志文章,评审


    authors: Murphy S,Peterson P,Iland H,Laszlo J

    更新日期:1997-01-01 00:00:00

  • Fc receptor blockade and immune thrombocytopenic purpura.

    abstract::Inhibition of antibody-coated platelet destruction in patients with immune thrombocytopenic purpura (ITP) is a well-known mechanism of treatment effect. A number of interventions that would ameliorate the thrombocytopenic effect of ITP patient plasma when infused into normal recipients were demonstrated in 1965. Subse...

    journal_title:Seminars in hematology

    pub_type: 杂志文章,评审


    authors: Bussel JB

    更新日期:2000-07-01 00:00:00

  • Treatment approach to newly diagnosed diffuse large B-cell lymphoma.

    abstract::Diffuse large B-cell lymphoma (DLBCL) is the most frequent subtype of non-Hodgkin lymphoma in western countries. High prognostic heterogeneity is observed among patients with DLBCL with long-term survival ranging from 30% to more than 90% according to clinic-biological prognostics such as the International Prognostic ...

    journal_title:Seminars in hematology

    pub_type: 杂志文章,评审


    authors: Bachy E,Salles G

    更新日期:2015-04-01 00:00:00

  • Safety profile of recombinant factor VIIa.

    abstract::Recombinant factor VIIa (rFVIIa; NovoSeven(R), Novo Nordisk, Bagsvaerd, Denmark) has been used for many years in the successful management of bleeding episodes in patients with hemophilia and inhibitors. More recently, rFVIIa has also shown considerable success as a hemostatic agent in trauma and surgery patients with...

    journal_title:Seminars in hematology

    pub_type: 杂志文章,评审


    authors: Roberts HR,Monroe DM 3rd,Hoffman M

    更新日期:2004-01-01 00:00:00

  • New anti-thrombotic agents: emphasis on hemorrhagic complications and their management.

    abstract::Our advanced knowledge of coagulation has led to the synthesis of novel procoagulant substances, such as recombinant activated factor VII (rFVIIa; NovoSeven, Novo Nordisk, Bagsvaerd, Denmark). Similarly, in-depth understanding of the interaction between anticoagulant proteins and their natural inhibitors has led to th...

    journal_title:Seminars in hematology

    pub_type: 杂志文章,评审


    authors: Ng HJ,Crowther MA

    更新日期:2006-01-01 00:00:00

  • Somatic characterization of pediatric acute myeloid leukemia using next-generation sequencing.

    abstract::Acute myeloid leukemia (AML) is a complex and heterogeneous disease with distinct age-associated genomic and epigenomic alterations. A large number of somatic karyotypic and molecular alterations have been identified in AML to date; however, very few predict outcome or identify potential therapeutic targets. Here we d...

    journal_title:Seminars in hematology

    pub_type: 杂志文章,评审


    authors: Schuback HL,Arceci RJ,Meshinchi S

    更新日期:2013-10-01 00:00:00

  • Targeted therapies in the treatment of Philadelphia chromosome-positive acute lymphoblastic leukemia.

    abstract::Imatinib mesylate (Gleevec, Novartis Pharmaceuticals Corp, East Hanover, NJ; Glivec, Novartis Pharma AG, Basel, Switzerland), a signal transduction inhibitor with preferential effects against the tyrosine kinase activity of the protein product of the ABL proto-oncogene, induced hematologic responses in >or=90% of pati...

    journal_title:Seminars in hematology

    pub_type: 杂志文章,评审


    authors: Hoelzer D,Gökbuget N,Ottmann OG

    更新日期:2002-10-01 00:00:00

  • Immune dysregulation in immune thrombocytopenia.

    abstract::Immune thrombocytopenia (ITP) is a bleeding disorder characterized by low platelet counts due to decreased platelet production as well as increased platelet destruction by autoimmune mechanisms. A shift toward Th1 and possibly Th17 cells together with impaired regulatory compartment, including T-regulatory (Tregs) and...

    journal_title:Seminars in hematology

    pub_type: 杂志文章,评审


    authors: Yazdanbakhsh K,Zhong H,Bao W

    更新日期:2013-01-01 00:00:00

  • Rare causes of hereditary iron overload.

    abstract::Iron is a vitally important element in mammalian metabolism because of its unsurpassed versatility as a biologic catalyst. However, when not appropriately shielded or when present in excess, iron plays a key role in the formation of extremely toxic oxygen radicals, which ultimately cause peroxidative damage to vital c...

    journal_title:Seminars in hematology

    pub_type: 杂志文章,评审


    authors: Ponka P

    更新日期:2002-10-01 00:00:00

  • Activity survey and historical perspective of autologous stem cell transplantation in Europe.

    abstract::Autologous hematopoietic stem cell transplantation (HSCT) has a long tradition in Europe. Initially developed as a tool to restore rapid remission or chronic phase in patients with advanced leukemia without a sibling donor, it evolved over the last three decades to be used as a standard tool in patients with malignanc...

    journal_title:Seminars in hematology

    pub_type: 历史文章,杂志文章


    authors: Gratwohl A

    更新日期:2007-10-01 00:00:00

  • Future strategies toward the cure of indolent B-cell malignancies. Immune recognition and antiself.

    abstract::Tumor cells from patients with B-cell malignancies exhibit a number of immunophenotypic characteristics that may be responsible for their survival. It has been shown, for example, that down-modulation of CD154 (CD40 ligand), which allows B cells to respond to T cells, may account for some of the immune defects of thes...

    journal_title:Seminars in hematology

    pub_type: 杂志文章,评审


    authors: Nadler LM

    更新日期:1999-10-01 00:00:00

  • Management of chronic myeloid leukemia: targets for molecular therapy.

    abstract::Chronic myeloid leukemia (CML) is a hematopoietic disorder characterized by malignant expansion of bone marrow stem cells. Currently, the only unequivocally curative treatment for CML is allogeneic stem cell transplant. Unfortunately, a large proportion of CML patients are ineligible for such treatment and alternative...

    journal_title:Seminars in hematology

    pub_type: 杂志文章,评审


    authors: Barnes DJ,Melo JV

    更新日期:2003-01-01 00:00:00

  • Management of the relapsed/refractory myeloma patient: strategies incorporating lenalidomide.

    abstract::The immunomodulatory drug (IMiD) lenalidomide is a more potent immunomodulator than thalidomide with respect to its effects on cytokine modulation and increased T-cell proliferation. Of all the IMiDs, clinical trial data are most mature for lenalidomide. In phase I studies, dose-limiting toxicities of lenalidomide wer...

    journal_title:Seminars in hematology

    pub_type: 杂志文章,评审


    authors: Richardson P

    更新日期:2005-10-01 00:00:00