Abstract:
:Imatinib mesylate and rituximab are molecularly targeted drugs against the BCR-ABL fusion protein and the CD20 antigen, respectively. Although these drugs have excellent anticancer effects, a major concern is drug resistance. We have investigated the case of a patient with Philadelphia chromosome-positive and CD20+ acute lymphocytic leukemia who acquired resistance to imatinib and rituximab. Imatinib therapy resulted in prompt cytogenetic remission, but resistance developed shortly thereafter. Sequencing of the kinase domain of the ABL gene and allele-specific polymerase chain reaction analysis revealed a point mutation resulting in an E255V substitution that was present before the therapy. After the patient received mild chemotherapy followed by rituximab administration, hematologic and cytogenetic remission was sustained for 5.5 months. The recurrent leukemic cells after the rituximab therapy showed not only the E255V mutation in the ABL gene but also loss of the CD20 antigen due to impaired transcription of the CD20 gene. The results of 2-color flow cytometry analysis showed that a small population of CD20(-) leukemic cells existed before the imatinib therapy. These results suggest that leukemic subclones carrying a genetic perturbation of the targeted molecules for both imatinib and rituximab were present before the therapies. The preexistence of primary resistant clones suggests the inability of combination therapy with 2 molecularly targeted drugs to overcome drug resistance in leukemia.
journal_name
Int J Hematoljournal_title
International journal of hematologyauthors
Hato T,Yamanouchi J,Tamura T,Hojo N,Niiya Y,Kohno M,Bando S,Yakushijin Y,Takada K,Sakai I,Yasukawa M,Fujita Sdoi
10.1532/ijh97.04033subject
Has Abstractpub_date
2004-07-01 00:00:00pages
62-6issue
1eissn
0925-5710issn
1865-3774journal_volume
80pub_type
杂志文章abstract:BACKGROUND:The chronic myeloproliferative diseases (CMPDs) include chronic myelogenous leukemia (CML), primary (essential) thrombocythemia (PT), agnogenic myeloid metaplasia (AMM), and polycythemia vera (PV). Certain hematological malignancies have a different prevalence in our country than in countries with Caucasian ...
journal_title:International journal of hematology
pub_type: 杂志文章
doi:10.1007/BF02982113
更新日期:2002-06-01 00:00:00
abstract::Hemophagocytic syndrome (HPS) is a clinicopathological reflection of uncontrolled activation of macrophages. To our knowledge, only a few cases of tuberculosis-associated HPS in hemodialysis have been reported in the English literature. We report a case of tuberculosis-associated HPS during hemodialysis. Bone marrow a...
journal_title:International journal of hematology
pub_type: 杂志文章
doi:10.1532/ijh97.a10315
更新日期:2004-05-01 00:00:00
abstract::Internal tandem duplication in the FLT3 gene (FLT3/ITD), which is found in patients with acute myeloid leukemia (AML), causes resistance to FLT3 inhibitors. We found that RUNX1, a transcription factor that regulates normal hematopoiesis, is up-regulated in patients with FLT3/ITD(+) AML. While RUNX1 can function as a t...
journal_title:International journal of hematology
pub_type: 杂志文章
doi:10.1007/s12185-015-1908-8
更新日期:2016-01-01 00:00:00
abstract::Allogeneic hematopoietic stem-cell transplantation (HSCT) for chronic granulomatous disease (CGD) with a reduced-intensity conditioning regimen can be expected to lead to less therapy-related mortality and late-onset impairment, whereas it has also been reported to increase the risk of unsustained mixed donor chimeris...
journal_title:International journal of hematology
pub_type: 杂志文章
doi:10.1007/s12185-007-0017-8
更新日期:2008-01-01 00:00:00
abstract::Spontaneous improvement (SI) occurs more frequently in children with chronic immune thrombocytopenia (cITP) than in adults. It is generally accepted that, with the exception of splenectomy, conventional medical approaches for cITP do not change the natural course of the disease. Previous studies on pediatric cITP have...
journal_title:International journal of hematology
pub_type: 杂志文章
doi:10.1007/s12185-012-1211-x
更新日期:2012-12-01 00:00:00
abstract::Inorganic polyphosphate (polyP) is abundant in biological organisms. PolyP is a major component of dense granules of human platelets and is secreted upon platelet activation. Studies from our lab and others have shown that polyP is a potent modulator of the blood clotting cascade, acting as a pro-hemostatic, prothromb...
journal_title:International journal of hematology
pub_type: 杂志文章,评审
doi:10.1007/s12185-012-1054-5
更新日期:2012-04-01 00:00:00
abstract::Autologous stem cell transplantation is considered the best post-induction therapy for multiple myeloma (MM). Therefore, therapy for myeloma should be chosen not only on the basis of efficacy, but also taking into account their impact on the hematopoietic stem cell compartment. We describe the case of a MM patient in ...
journal_title:International journal of hematology
pub_type: 杂志文章
doi:10.1007/s12185-009-0354-x
更新日期:2009-07-01 00:00:00
abstract::The changes of the FVIII binding capacity of vWF after the infusion of FVIII/vWF concentrate was studied in two patients with type 2N vWD, and also during pregnancy in one of them. After infusion of FVIII or DDAVP to the patients, FVIII:C in plasma increased as expected, but it then decreased, with a markedly short ha...
journal_title:International journal of hematology
pub_type: 杂志文章
doi:10.1016/0925-5710(96)00470-7
更新日期:1996-08-01 00:00:00
abstract::We report here the successful treatment of cold agglutinin-associated refractory hemolysis with bortezomib in a patient with Waldenström's macroglobulinemia (WM). A 78-year-old man was referred to our hospital with cold hemagglutinemia of unknown cause. Laboratory examination revealed a hemoglobin concentration of 6.9...
journal_title:International journal of hematology
pub_type: 杂志文章
doi:10.1007/s12185-015-1775-3
更新日期:2015-08-01 00:00:00
abstract::Human granulocyte colony-stimulating factor (G-CSF) receptor cDNA was introduced into the erythroleukemic cell line K562, which normally does not express the receptor, using lipofection transfection of a G-CSF receptor expression plasmid vector. Transfected cells expressed the receptor with a dissociation constant of ...
journal_title:International journal of hematology
pub_type: 杂志文章
doi:10.1016/0925-5710(95)00352-s
更新日期:1995-02-01 00:00:00
abstract::The phagocyte nicotinamide adenine dinucleotide phosphate (NADPH) oxidase plays a crucial role in host defense by neutrophils and macrophages. When cells ingest invading microbes, this enzyme becomes activated to reduce molecular oxygen to superoxide, a precursor of microbicidal oxidants, in the phagosome. The catalyt...
journal_title:International journal of hematology
pub_type: 杂志文章,评审
doi:10.1532/IJH97.06133
更新日期:2006-10-01 00:00:00
abstract::Ecotropic viral integration site-1 (EVI-1) has been recognized as one of the dominant oncogenes associated with murine and human myeloid leukemia. Recent clinical studies demonstrated that high EVI-1 expression was an independent negative prognostic indicator of survival in leukemia patients. In addition, gene-targeti...
journal_title:International journal of hematology
pub_type: 杂志文章,评审
doi:10.1007/s12185-010-0618-5
更新日期:2010-06-01 00:00:00
abstract::Nuclear factor-kappa B (NF-κB) is a multipotent transcription factor that plays a pivotal role in immune reactions, inflammation, and possibly hematopoiesis as well. Mobilization of neutrophilic granulocytes during inflammation is a highly regulated process, but one that is incompletely understood. We studied the in v...
journal_title:International journal of hematology
pub_type: 杂志文章
doi:10.1007/s12185-014-1598-7
更新日期:2014-08-01 00:00:00
abstract::X-linked lymphoproliferative disease (XLP) is an inherited immunodeficiency characterized by an extreme susceptibility to Epstein-Barr virus (EBV) infection. Patients with XLP mainly present with the 3 clinical manifestations of fulminant infectious mononucleosis, lymphoproliferative disorder, and dysgammaglobulinemia...
journal_title:International journal of hematology
pub_type: 杂志文章
doi:10.1532/IJH97.05020
更新日期:2005-07-01 00:00:00
abstract::Allogeneic hematopoietic stem cell transplantation (HSCT) and tyrosine kinase inhibitor have revolutionized the treatment of patients with chronic myeloid leukemia (CML). In this study, the clinical impact of HSCT and imatinib mesylate (IM) was retrospectively analyzed in 28 children with CML treated in our institutes...
journal_title:International journal of hematology
pub_type: 杂志文章,多中心研究
doi:10.1007/s12185-010-0764-9
更新日期:2011-02-01 00:00:00
abstract::Patients with mild/moderate hemophilia (H)A, acquired HA (AHA) and lupus anticoagulants (LA), have prolonged aPTTs with low levels of factor (F)VIII activity, but the differentiation of these disorders is complex and time consuming. We established an approach to quickly differentiate these disorders using comprehensiv...
journal_title:International journal of hematology
pub_type: 杂志文章
doi:10.1007/s12185-016-2108-x
更新日期:2017-02-01 00:00:00
abstract::Diffuse follicular lymphoma (FL) variant is a rare condition that shows distinctive clinical, morphological, immunophenotypic, and molecular features that distinguish it from classical FL. Diffuse FL variant is characterized by a predominantly diffuse growth pattern, absence of the t (14;18) IGH/BCL2 translocation, CD...
journal_title:International journal of hematology
pub_type: 信件
doi:10.1007/s12185-020-02901-1
更新日期:2020-08-01 00:00:00
abstract::A 56-year-old woman with acute myelomonocytic leukemia underwent myeloablative allogeneic hematopoietic stem cell transplantation (allo-SCT) from a matched unrelated donor in her first complete remission (CR). Veno-occlusive disease (VOD) prophylaxis consisted of low-dose heparin and ursodeoxycholic acid. Graft-versus...
journal_title:International journal of hematology
pub_type: 杂志文章
doi:10.1007/s12185-009-0440-0
更新日期:2009-12-01 00:00:00
abstract::B-cell diseases are classified on the basis of the normal differentiation stages. We report here a case of a patient with a long history of leukocytosis, splenomegaly without lymphadenopathy, and hyperviscosity symptoms. Clinically, the patient's diagnosis was leukemic Waldenstrom macroglobulinemia. Chromosomal analys...
journal_title:International journal of hematology
pub_type: 杂志文章
doi:10.1007/BF02982811
更新日期:2002-12-01 00:00:00
abstract::The Wilms tumor gene WT1 is expressed in leukemias and various kinds of solid tumors, including lung and breast cancer, and exerts an oncogenic function in these malignancies, suggesting that WT1 protein is a novel, overexpressed tumor antigen. The WT1 protein, in fact, is an attractive tumor rejection antigen in anim...
journal_title:International journal of hematology
pub_type: 杂志文章,评审
doi:10.1007/BF02982574
更新日期:2002-08-01 00:00:00
abstract::We describe a patient with persistent pure red cell aplasia due to human parvovirus B19 (HPVB19) infection during immunosuppressive therapy for refractory autoimmune hemolytic anemia (AIHA). The patient had been given corticosteroid (CS) and/or azathioprine for AIHA. During the course of treatment, reticulocyte count ...
journal_title:International journal of hematology
pub_type: 杂志文章
doi:10.1532/ijh97.04017
更新日期:2004-10-01 00:00:00
abstract::Shwachman-Diamond syndrome (SDS) is a rare congenital disorder featuring exocrine pancreatic insufficiency, growth retardation, and bone marrow dysfunction. Reports suggest that nearly 25% of all cases are complicated with leukemia. Although stem cell transplantation is the sole option for these patients, successful r...
journal_title:International journal of hematology
pub_type: 杂志文章,评审
doi:10.1532/ijh97.03103
更新日期:2004-02-01 00:00:00
abstract::In order to better understand the biology of adult T cell leukemia (ATL), we aimed to establish a novel method, which allows the primary growth of ATL cells using a co-culture system with murine bone marrow-derived stromal cells, MS-5. ATL cells grew in close contact with MS-5 layers and formed so-called "cobblestone ...
journal_title:International journal of hematology
pub_type: 杂志文章
doi:10.1007/s12185-008-0207-z
更新日期:2008-12-01 00:00:00
abstract::Pulmonary alveolar proteinosis (PAP) is a rare disorder characterized by the abnormal accumulation of alveolar surfactant protein in alveolar spaces. We report herein a rare case of myelodysplastic syndrome (MDS-RAEB) complicated by severe PAP, and successful allogeneic bone marrow transplantation (BMT) for both disor...
journal_title:International journal of hematology
pub_type: 杂志文章
doi:10.1007/s12185-009-0404-4
更新日期:2009-10-01 00:00:00
abstract::A 67-year-old man suffered from a left cervical lymph node swelling and tenderness. Biopsy of the cervical lymph node showed pleomorphic large cells containing large atypical nuclei. Immunohistochemical stains of these cells were positive for CD30, but negative for CD3 and CD20. After the biopsy, his left cervical ski...
journal_title:International journal of hematology
pub_type: 信件
doi:10.1007/s12185-010-0675-9
更新日期:2010-10-01 00:00:00
abstract::Immature-type CD56(+) natural killer (NK)-cell neoplasms are classified as either myeloid/NK-cell precursor acute leukemia or blastic NK-cell lymphoma. We identified two cases of immature-type CD56(+) NK-cell neoplasms that were not categorizable as either of these entities. The first case involved a 74-year-old woman...
journal_title:International journal of hematology
pub_type: 杂志文章
doi:10.1007/s12185-008-0233-x
更新日期:2009-03-01 00:00:00
abstract::Elderly/comorbid patients with chronic lymphocytic leukemia (CLL) require low-toxicity treatments. Internationally, the standard treatment for such patients is chlorambucil and an anti-CD20 therapy; however, chlorambucil is not approved in Japan. The aim of the present study was to evaluate the safety, efficacy and ph...
journal_title:International journal of hematology
pub_type: 杂志文章
doi:10.1007/s12185-017-2233-1
更新日期:2017-08-01 00:00:00
abstract::A 47-year-old woman presented with severe hemolytic uremic syndrome (HUS) followed by heart failure. An echocardiogram showed an ejection fraction of 20%, and a cardiac catheterization followed by a myocardial histologic evaluation demonstrated dilated cardiomyopathy. Plasma exchange and hemodialysis were performed re...
journal_title:International journal of hematology
pub_type: 杂志文章
doi:10.1532/IJH97.E0713
更新日期:2007-11-01 00:00:00
abstract::The heart is a rare primary site of lymphoma, and cardiac involvement is thought to bring a poorer prognosis. A framework of known clinical presentations, diagnostic features, disease complications, treatments, and outcomes to improve prognostication was constructed by a systematic review in 2011. However, some aspect...
journal_title:International journal of hematology
pub_type: 杂志文章
doi:10.1007/s12185-020-02881-2
更新日期:2020-07-01 00:00:00
abstract::Hematologic malignancies have historically been characterized by morphologic, immunophenotypic, molecular, and genetic features. However, morphologically identical tumors can have clearly distinct clinical outcomes, suggesting underlying biological heterogeneity. Recent advances in microarray technology have helped th...
journal_title:International journal of hematology
pub_type: 杂志文章,评审
doi:10.1532/ijh97.04133
更新日期:2004-12-01 00:00:00