Why do chronic myelogenous leukemia stem cells survive allogeneic stem cell transplantation or imatinib: does it really matter?

Abstract:

:It is generally accepted that allogeneic stem cell transplantation can 'cure' chronic myelogenous leukemia (CML), although occasional patients relapse more than 10 years after the transplant procedure. Such cures presumably result from the combined effects of leukemia stem cells (LSCs) of the conditioning regimen and the graft-vs.-leukemia (GvL) effect mediated by donor-derived T lymphocytes. The advent of imatinib has revolutionized the management of patients with CML, but much evidence suggests that it does not eradicate all LSCs, which theoretically remain a potential source of relapse to chronic phase or advanced phase disease. Moreover, sub-clones of Philadelphia-positive cells bearing mutations that code for amino-acid substitutions in the Bcr-Abl kinase domain can be identified in patients receiving treatment with imatinib and are associated with varying degrees of resistance to this agent. In the present review, we postulate that LSCs, similar to their normal counterparts, may alternate between cycling and quiescent modes. In the cycling mode, they may express Bcr-Abl protein and be susceptible to the acquisition of additional mutations, whereas, in the quiescent mode, they may express little or no Bcr-Abl oncoprotein, cannot acquire additional mutations and are unaffected by imatinib. Thus, a patient who starts treatment early in the natural history of CML, and who responds to imatinib clinically, may not have had the opportunity to acquire additional mutations in LSCs. In this case, the persistence long-term of quiescent 'non-mutated' LSCs despite imatinib treatment might be consistent with freedom from relapse to chronic or advanced phase disease, provided that they remain vulnerable to imatinib when they are recruited into cycle. Conversely, when imatinib resistant Philadelphia-positive sub-clones predominate, this is likely to be due to the recruitment to hematopoiesis of quiescent stem cells that had been in cycle before administration of imatinib and that had acquired additional mutations; in such cases, the best approach to eradication of residual LSCs might be to target expressed proteins thought to be targets for the GvL effect.

journal_name

Leuk Lymphoma

journal_title

Leukemia & lymphoma

authors

Goldman J,Gordon M

doi

10.1080/10428190500407996

keywords:

subject

Has Abstract

pub_date

2006-01-01 00:00:00

pages

1-7

issue

1

eissn

1042-8194

issn

1029-2403

pii

H57841JV43U26245

journal_volume

47

pub_type

杂志文章,评审
  • The characteristics and outcomes of patients with multiple myeloma dual refractory or intolerant to bortezomib and lenalidomide in the era of carfilzomib and pomalidomide.

    abstract::Patients with multiple myeloma who are refractory or intolerant to both bortezomib and lenalidomide have a poor prognosis. Next-generation therapies carfilzomib and pomalidomide have shown promising activity in this dual refractory population. Here we describe the clinical characteristics and ascertain the effects of ...

    journal_title:Leukemia & lymphoma

    pub_type: 杂志文章

    doi:10.3109/10428194.2013.803547

    authors: Wang TF,Ahluwalia R,Fiala MA,Trinkaus KM,Cox DP,Jaenicke M,Moliske CC,Carson KR,Wildes TM,Tomasson MH,Stockerl-Goldstein KE,Vij R

    更新日期:2014-02-01 00:00:00

  • R-CHOP(-like) treatment of diffuse large B-cell lymphoma significantly reduces CT-assessed vertebral bone density: a single center study of 111 patients.

    abstract::Treatment of diffuse large B-cell lymphoma (DLBCL) with R-CHOP(-like) regimens include large cumulative doses of prednisolone. In this retrospective study, we evaluated changes in vertebral bone density (VD) in DLBCL patients by measuring CT-ascertained Hounsfield units (HU) at the L3 level. In total, 111 patients dia...

    journal_title:Leukemia & lymphoma

    pub_type: 杂志文章

    doi:10.1080/10428194.2016.1233543

    authors: Svendsen P,Shekhrajka N,Nielsen KL,Vestergaard P,Poulsen MØ,Vistisen AK,Munksgaard PS,Severinsen MT,Jensen P,Johnsen HE,Jakobsen LH,Bøgsted M,Frøkjær JB,El-Galaly TC

    更新日期:2017-05-01 00:00:00

  • Suicide gene-mediated modulation of graft-versus-host disease.

    abstract::The development of suicide genes and progress in retroviral gene transfer to T-cells open new perspectives for the treatment of graft-versus-host disease (GVHD) after allogeneic bone marrow transplantation (BMT) for leukemia and lymphoma. Indeed, suicide genes that metabolize inactive prodrugs into compounds toxic for...

    journal_title:Leukemia & lymphoma

    pub_type: 杂志文章,评审

    doi:10.3109/10428199909058474

    authors: Cohen JL,Boyer O,Thomas-Vaslin V,Klatzmann D

    更新日期:1999-08-01 00:00:00

  • Superior outcome of patients with favorable-risk acute myeloid leukemia using consolidation with autologous stem cell transplantation.

    abstract::Autologous stem cell transplantation (ASCT), intensifying anti-leukemic effects without significant treatment-related mortality (TRM), is particularly appealing in AML with favorable genetic/molecular profile. This study retrospectively evaluated the outcomes of post-remission treatment in consecutive favorable-risk A...

    journal_title:Leukemia & lymphoma

    pub_type: 杂志文章

    doi:10.1080/10428194.2019.1594214

    authors: Beyar-Katz O,Lavi N,Ringelstein-Harlev S,Henig I,Yehudai-Ofir D,Haddad N,Fineman R,Ofran Y,Nov Y,Sahar D,Moustafa-Hawash N,Rowe JM,Zuckerman T

    更新日期:2019-10-01 00:00:00

  • Disease features in acute myeloid leukemia with t(8;21)(q22;q22). Influence of age, secondary karyotype abnormalities, CD19 status, and extramedullary leukemia on survival.

    abstract::Over a period of 14 years, 50 patients (12 children and 38 adults) of whom 46 had acute myeloid leukemia (AML) and 4 had myelodysplastic syndrome characterized by the t(8;21)(q22;q22) translocation were referred to the Royal Marsden Hospital. The clinicopathological features of these cases were analyzed to determine t...

    journal_title:Leukemia & lymphoma

    pub_type: 杂志文章

    doi:10.3109/10428190009054882

    authors: Rege K,Swansbury GJ,Atra AA,Horton C,Min T,Dainton MG,Matutes E,Durosinmi M,Treleaven JG,Powles RL,Catovsky D

    更新日期:2000-12-01 00:00:00

  • Nuclear NF-ATp is a hallmark of unstimulated B cells from B-CLL patients.

    abstract::B lymphocytes from the peripheral blood of patients with chronic lymphocytic leukaemia (CLL) were analysed for the nuclear presence and DNA binding of a panel of transcription factors which are involved in the gene control of lymphoid cells. The following transcription factors were studied: the Octamer factors Oct-1 a...

    journal_title:Leukemia & lymphoma

    pub_type: 杂志文章

    doi:10.3109/10428199609054868

    authors: Schuh K,Avots A,Tony HP,Serfling E,Kneitz C

    更新日期:1996-11-01 00:00:00

  • Molecular remission following high-dose hydroxyurea and fludarabine plus cytarabine in a patient with simultaneous acute myeloid leukemia and low-grade lymphoma.

    abstract::The occurrence of acute myeloid leukemia (AML) as a secondary tumor has been frequently reported in patients who received various chemotherapy regimens for hematologic malignancies wile the concomitant development of chronic lymphoproliferative diseases (CLD) and AML in previously untreated patients is extremely rare....

    journal_title:Leukemia & lymphoma

    pub_type: 杂志文章

    doi:10.3109/10428190109097666

    authors: Montefusco E,Fazi F,Cordone I,Ariola C,Nanni M,Spadea A,Spiriti MA,Fenu S,Mandelli F,Petti MC

    更新日期:2001-02-01 00:00:00

  • Autocrine and paracrine regulation of neoplastic cell growth in hairy cell leukemia.

    abstract::Hairy cell leukemia (HCL), a rare haematological disorder of B-cell origin, mainly presents with bone marrow infiltration, haematopoietic insufficiency, and splenomegaly. In some cases, osteolytic lesions can be observed. Many of these clinical features, especially haematopoietic insufficiency and osteolytic lesions a...

    journal_title:Leukemia & lymphoma

    pub_type: 杂志文章,评审

    doi:10.3109/10428199509056850

    authors: Schmid M,Porzsolt F

    更新日期:1995-05-01 00:00:00

  • Human T-leukemia and T-lymphoma express glutamate receptor AMPA GluR3, and the neurotransmitter glutamate elevates the cancer-related matrix-metalloproteinases inducer CD147/EMMPRIN, MMP-9 secretion and engraftment of T-leukemia in vivo.

    abstract::Glutamate is the major excitatory neurotransmitter of the nervous system. We previously found that glutamate activates normal human T-cells, inducing their adhesion and chemotaxis, via its glutamate receptors of the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) subtype 3 (GluR3) expressed in these ce...

    journal_title:Leukemia & lymphoma

    pub_type: 杂志文章

    doi:10.1080/10428190902878448

    authors: Ganor Y,Grinberg I,Reis A,Cooper I,Goldstein RS,Levite M

    更新日期:2009-06-01 00:00:00

  • Ten years and counting: so what do we know about t(4;14)(p16;q32) multiple myeloma.

    abstract::Multiple myeloma is a genetically heterogenous disease with a wide variety of characterized genetic aberrations. Until recently, the impact of these aberrations on patient outcome was not known. However, in the last 5-10 years, several genetic markers have been linked to patient outcome. One of the strongest predictor...

    journal_title:Leukemia & lymphoma

    pub_type: 杂志文章,评审

    doi:10.1080/10428190600822128

    authors: Keats JJ,Reiman T,Belch AR,Pilarski LM

    更新日期:2006-11-01 00:00:00

  • Clonality assays and megakaryocyte culture techniques in essential thrombocythemia.

    abstract::The development of techniques permitting in vitro growth of human megakaryocytes progenitors and more recently identification of the proto oncogene c-mpl (Mpl-R) and its ligand (Mpl-L) have created new opportunities for studying pathophysiology of E.T. Plasma or serum of E.T. patients was unable to overestimulate MK c...

    journal_title:Leukemia & lymphoma

    pub_type: 杂志文章,评审

    doi:10.3109/10428199609074358

    authors: Yan L,Elkassar N,Gardin C,Briere J

    更新日期:1996-09-01 00:00:00

  • Increased serum soluble Fas ligand associated with recurrent B-cell non-Hodgkin's lymphoma after autologous peripheral blood stem cell transplantation.

    abstract::Fas-ligand (FasL) is a member of the tumor necrosis factor family and transmits apoptotic cell death signal by binding to its receptor, Fas. FasL is expressed on the cell surface of activated T-cell and natural killer (NK) cell. It has been shown that the FasL can be released from the cell surface by metalloproteinase...

    journal_title:Leukemia & lymphoma

    pub_type: 杂志文章

    doi:10.3109/10428199909058494

    authors: Kanda Y,Chiba S,Tanaka Y,Kami M,Saito T,Izutsu K,Asai T,Yuji K,Ogawa S,Honda H,Mitani K,Usuki K,Urabe A,Shirakawa K,Yatomi T,Nakamura N,Yazaki Y,Hirai H

    更新日期:1999-08-01 00:00:00

  • New insights into the regulation of ICAM-1 gene expression.

    abstract::Cell-cell adhesion is critical in the generation of effective immune responses and is dependent upon the expression of a variety of cell surface receptors. Intercellular adhesion molecule-1 (ICAM-1; CD54) is an inducible cell surface glycoprotein expressed at a low level on a subpopulation of hematopoietic cells, vasc...

    journal_title:Leukemia & lymphoma

    pub_type: 杂志文章,评审

    doi:10.3109/10428199609051611

    authors: Ohh M,Takei F

    更新日期:1996-01-01 00:00:00

  • Dipeptidyl peptidase IV: serum activity and expression on lymphocytes in different hematological malignancies.

    abstract::The aim of this research was to determine the serum dipeptidyl peptidase IV (DPPIV) activity as well as the percentages of CD26 + lymphocytes and CD26 + overall white blood cells in patients with hematological malignancies: non-Hodgkin lymphoma (NHL), Hodgkin lymphoma (HL), leukemia, plasmacytoma and multiple myeloma,...

    journal_title:Leukemia & lymphoma

    pub_type: 杂志文章

    doi:10.3109/10428194.2013.782611

    authors: Matić IZ,Đorđević M,Đorđić M,Grozdanić N,Damjanović A,Kolundžija B,Vidović A,Bila J,Ristić S,Mihaljević B,Tomin D,Milanović N,Ristić D,Purić M,Gavrilović D,Cordero OJ,Juranić ZD

    更新日期:2013-12-01 00:00:00

  • Genetic changes including gene copy number alterations and their relation to prognosis in childhood acute myeloid leukemia.

    abstract::We studied a series of 68 subjects diagnosed with childhood acute myeloid leukemia (AML) using conventional cytogenetics and fluorescence in situ hybridization (FISH), polymerase chain reaction (PCR) to analyze mutations in FLT3 and NPM1 genes, and/or array comparative genomic hybridization (CGH). Cytogenetic/FISH abn...

    journal_title:Leukemia & lymphoma

    pub_type: 杂志文章

    doi:10.3109/10428190903350397

    authors: Armengol G,Canellas A,Alvarez Y,Bastida P,Toledo JS,Pérez-Iribarne Mdel M,Camós M,Tuset E,Estella J,Coll MD,Caballín MR,Knuutila S

    更新日期:2010-01-01 00:00:00

  • Ferritin as prognostic marker in multiple myeloma patients undergoing autologous transplantation.

    abstract::Serum ferritin reflects body iron stores, but this correlation is dissociated in inflammation. Ferritin has been shown to be prognostically relevant in breast cancer and in patients with hematologic malignancies undergoing autologous or allogeneic stem cell transplantation. In the present study, we evaluated the progn...

    journal_title:Leukemia & lymphoma

    pub_type: 杂志文章

    doi:10.3109/10428194.2014.891025

    authors: Strasser-Weippl K,Ludwig H

    更新日期:2014-11-01 00:00:00

  • Gravin gene expression in acute leukaemias: clinical importance and review of the literature.

    abstract::The aim of this study was to determine the expression of Gravin (a tumor suppressor gene belonging to the A kinase anchoring protein family) in samples of acute leukaemia and to explore its association with the prognosis. The study group consisted of 162 people (137 patients with acute leukaemia and 25 volunteers as c...

    journal_title:Leukemia & lymphoma

    pub_type: 杂志文章,评审

    doi:10.1080/10428190701377055

    authors: Yildirim M,Paydas S,Tanriverdi K,Seydaoglu G,Disel U,Yavuz S

    更新日期:2007-06-01 00:00:00

  • Augmented myeloablative conditioning with thiotepa in acute myeloid leukemia - improved outcomes with similar toxicity.

    abstract::Myeloablative doses of busulfan (Bu) with fludarabine (Flu) have reduced toxicity, however, limited by an increased relapse rate. We aimed to improve outcome of Flu-Bu regimen by augmentation with thiotepa (TT) (10 mg/kg). Eighty-nine patients with AML, 44 patients conditioned with Flu-Bu (group 1), and 45 patients au...

    journal_title:Leukemia & lymphoma

    pub_type: 杂志文章

    doi:10.1080/10428194.2018.1510495

    authors: Sheth V,Nachmias B,Grisariu S,Avni B,Or R,Shapira M

    更新日期:2019-03-01 00:00:00

  • Combination of cytarabine and topotecan in patients treated for acute myeloid leukemia with persistent disease after frontline induction.

    abstract::After a first course of induction chemotherapy, 30-40% of patients with acute myeloid leukemia (AML) do not achieve a complete response (CR). A second course of an anthracycline and intermediate-dose cytarabine (IDAC) allows a significant number of patients with persistent AML at day 14 to finally achieve a CR. We hyp...

    journal_title:Leukemia & lymphoma

    pub_type: 杂志文章

    doi:10.3109/10428194.2012.685733

    authors: Prébet T,Jean E,Autret A,Charbonnier A,Rey J,Etienne A,D'incan E,Fürst S,Arnoulet C,Blaise D,Vey N

    更新日期:2012-11-01 00:00:00

  • MicroRNAs and tRNA-derived fragments predict the transformation of myelodysplastic syndromes to acute myeloid leukemia.

    abstract::Myelodysplastic syndromes (MDS) are clonal hematopoietic disorders of the elderly that carry an increased risk of progression to acute myeloid leukemia (AML). Since small non-coding RNAs (sRNAs), including microRNA (miRNAs), act as regulators of cellular differentiation, we hypothesized that changes to sRNAs might be ...

    journal_title:Leukemia & lymphoma

    pub_type: 杂志文章

    doi:10.1080/10428194.2016.1272680

    authors: Guo Y,Strickland SA,Mohan S,Li S,Bosompem A,Vickers KC,Zhao S,Sheng Q,Kim AS

    更新日期:2017-09-01 00:00:00

  • Regression of a plasmablastic lymphoma in a patient with HIV on highly active antiretroviral therapy.

    abstract::We describe an HIV-infected 44-year-old man who presented 1 month after discontinuation of HAART therapy with a large mass extending from the mediastinum, enclosing the heart and extending through the diaphragm to the epigastric region. Biopsies subsequently revealed a highly aggressive non-Hodgkin's lymphoma (NHL) pr...

    journal_title:Leukemia & lymphoma

    pub_type: 杂志文章

    doi:10.1080/10428190290006260

    authors: Nasta SD,Carrum GM,Shahab I,Hanania NA,Udden MM

    更新日期:2002-02-01 00:00:00

  • Outcome determinants of fusariosis in a tertiary care cancer center: the impact of neutrophil recovery.

    abstract::Factors associated with failure of antifungal therapy were examined in 42 cancer patients with fusariosis (1987-1997). Thirty-six patients (86%) had leukemia and 39 (93%) were neutropenic. Disseminated infection was the most common presentation. The majority (83%) received amphotericin B-based therapy. Thirty patients...

    journal_title:Leukemia & lymphoma

    pub_type: 杂志文章

    doi:10.1080/1042819031000149386

    authors: Kontoyiannis DP,Bodey GP,Hanna H,Hachem R,Boktour M,Girgaway E,Mardani M,Raad II

    更新日期:2004-01-01 00:00:00

  • Post-transplantation lymphoproliferative disease in Chinese: the Queen Mary Hospital experience in Hong Kong.

    abstract::Post-transplantation lymphoproliferative disease (PTLD) is an unique iatrogenic complication after bone marrow transplantation (BMT) and solid organ transplantation (SOTx). The pattern of EBV related lymphoma in Chinese is different from Caucasians. We surveyed the incidence, clinical and pathological spectrum of PTLD...

    journal_title:Leukemia & lymphoma

    pub_type: 杂志文章

    doi:10.1080/10428190290033341

    authors: Au WY,Lie AK,Kwong YL,Shek TW,Hawkins BR,Lai KN,Tang SC,Lo CM,Fan ST,Liu CL,Chan GC,Chau EM,Chiu SW,Liang R

    更新日期:2002-07-01 00:00:00

  • Clinical implications of aberrant TSG101 transcripts in acute myeloblastic leukemia.

    abstract::Tsg101 is a mouse tumor suppressor gene whose homozygous deletion produces transformation of NIH3T3 cells and leads to metastases in nude mice. The human homologue of the gene, TSG101, is localized in chromosome 11p15.1-p15.2. Reduced TSG101 expression may cause the defect of the cell cycle checkpoint that leads to ge...

    journal_title:Leukemia & lymphoma

    pub_type: 杂志文章

    doi:10.3109/10428190009148393

    authors: Lin SF,Lin PM,Liu TC,Chang JG,Sue YC,Chen TP

    更新日期:2000-02-01 00:00:00

  • Lack of CD54 expression and mutation of p53 gene relate to the prognosis of childhood Burkitt's lymphoma.

    abstract::Expression of the intercellular adhesion molecule-1 (CD54) as well as the mutations of p53 gene were studied in childhood Burkitt's lymphoma (BL). Expression of CD54 was identified in 6 of 15 fresh BL cases. Mutations of p53 gene, analyzed by polymerase chain reaction-single stranded chain polymorphism followed by seq...

    journal_title:Leukemia & lymphoma

    pub_type: 杂志文章

    doi:10.3109/10428199609093443

    authors: Kaneko H,Sugita K,Kiyokawa N,Iizuka K,Takada K,Saito M,Yoshimoto K,Itakura M,Kokai Y,Fujimoto J

    更新日期:1996-05-01 00:00:00

  • Fixed-dose pegfilgrastim is safe and allows neutrophil recovery in patients with non-Hodgkin's lymphoma.

    abstract::Twenty-nine patients with non-Hodgkin's lymphoma received a single subcutaneous injection of 6 mg pegfilgrastim approximately 24 h after the start of CHOP chemotherapy. The safety of pegfilgrastim in this patient population was determined by reports of adverse events. The pharmacokinetics of pegfilgrastim were charact...

    journal_title:Leukemia & lymphoma

    pub_type: 杂志文章,多中心研究

    doi:10.1080/1042819031000063462

    authors: George S,Yunus F,Case D,Yang BB,Hackett J,Shogan JE,Meza LA,Neumann TA,Liang BC

    更新日期:2003-10-01 00:00:00

  • Hodgkin's disease: basing treatment decisions on prognostic factors.

    abstract::The purpose of this study was to review the current status of risk factor assessment in Hodgkin's disease (HD) clinically useful for managing this disease. Regarding database retrieval and selection a literature search restricted to English-language articles, abstracts, book chapters and reports published between 1980...

    journal_title:Leukemia & lymphoma

    pub_type: 杂志文章,评审

    doi:10.3109/10428199509056826

    authors: Faguet GB

    更新日期:1995-04-01 00:00:00

  • Hyperthyroidism six years post-BMT for acute myeloblastic leukemia in a patient on long-term lithium therapy for bipolar affective disorder.

    abstract::Lithium is commonly used to treat bipolar affective disorder. It is well known to adversely affect thyroid function, most commonly causing hypothyroidism. Hyperthyroidism is a rare complication. Similarly, total body irradiation (TBI) associated with BMT is well known to affect thyroid function frequently causing hypo...

    journal_title:Leukemia & lymphoma

    pub_type: 杂志文章

    doi:10.1080/10428190310001617286

    authors: Law A,Rifkind J,Rosen F,Lipton JH

    更新日期:2004-04-01 00:00:00

  • The anti-leukemic and lipid lowering effects of imatinib are not hindered by statins in CML: a retrospective clinical study and in vitro assessment of lipid-genes transcription.

    abstract::Imatinib, which has revolutionized chronic myeloid leukemia (CML) treatment, was suggested to improve lipid profile. Statins, a dyslipidemia drug, were reported to potentiate imatinib's antileukemic effect. However, analysis of imatinib combined with statins is lacking. We have retrospectively analyzed the normalizati...

    journal_title:Leukemia & lymphoma

    pub_type: 杂志文章

    doi:10.1080/10428194.2016.1228928

    authors: Ellis M,Krashin E,Hamburger-Avnery O,Gan S,Elis A,Ashur-Fabian O

    更新日期:2017-05-01 00:00:00

  • Prognostic relevance of DHAP dose-density in relapsed Hodgkin lymphoma: an analysis of the German Hodgkin-Study Group.

    abstract::Only 50% of patients with relapsed Hodgkin lymphoma (HL) can be cured with intensive induction chemotherapy, followed by high-dose chemotherapy (HDCT) and autologous stem cell transplant (ASCT). Based on the results of the HDR2 trial two courses of DHAP and subsequent HDCT/ASCT are the current standard of care in rela...

    journal_title:Leukemia & lymphoma

    pub_type: 杂志文章,多中心研究,随机对照试验

    doi:10.3109/10428194.2015.1083561

    authors: Sasse S,Alram M,Müller H,Smardová L,Metzner B,Doehner H,Fischer T,Niederwieser DW,Schmitz N,Schäfer-Eckart K,Raemaekers JM,Schmalz O,Tresckow BV,Engert A,Borchmann P

    更新日期:2016-05-01 00:00:00