Interaction of acute leukemia cells with the bone marrow microenvironment: implications for control of minimal residual disease.


:There is increasing evidence for an interaction between acute leukemia cells and the microenvironment of the bone marrow. Blast cells from cases of acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL) bind to cellular and extracellular matrix components of the bone marrow stroma. In AML, adhesion to stroma is mediated by the combined action of beta 1 (principally VLA-4) and beta 2 integrins, while in precursor-B ALL VLA-4 and VLA-5 integrins play a major role. Adhesion molecules such as CD31, CD44, non-beta 1, beta 2 integrins, growth factor receptors such as c-kit, and other molecules are also likely to play a role. Binding of acute leukemia blasts to ligands on stroma has several pathophysiological consequences. Stromal contact is able to inhibit programmed cell death (apoptosis) in a proportion of cases of both AML and ALL. In ALL, diffusible molecules derived from stroma appear to contribute. Marrow stroma also plays a part in regulating leukemic cell proliferation. While this is partly due to stromal production of hemopoietic growth factors, in soluble or transmembrane form or bound to extracellular matrix, signalling mediated directly by binding of adhesion molecules on leukemic cells may also have a role. Contact of ALL blasts with marrow fibroblasts is followed by migration of leukemic cells, utilizing VLA-4 and VLA-5 integrins, potentially allowing homing of blasts to favourable microenvironmental sites, or controlling egress into the circulation. AML cells compete for stromal binding sites with natural killer cells and cytotoxic lymphocytes, which are known to inhibit their clonogenic growth. We speculate that these complex interactions between leukemic blasts, cellular and matrix components of stroma, and cytotoxic lymphocytes, play a critical role in determining the fate of small numbers of leukemic cells surviving after cytotoxic chemotherapy.


Leuk Lymphoma


Leukemia & lymphoma


Bradstock KF,Gottlieb DJ




Has Abstract


1995-06-01 00:00:00












  • Clinical applicability of proposed algorithm for identifying individuals at risk for hereditary hematologic malignancies.

    abstract::Multiple genes have been identified to cause hereditary predispositions to hematologic malignancies, and characterized by an increased risk to develop myelodysplastic syndromes (MDS), acute myeloid leukemia (AML), and/or aplastic anemia (AA). Referral algorithms for patients who may be at higher risk have been propose...

    journal_title:Leukemia & lymphoma

    pub_type: 杂志文章


    authors: Clifford M,Bannon S,Bednar EM,Czerwinski J,Davis J,Dunnington L,Shahrukh Hashmi S,DiNardo CD

    更新日期:2019-12-01 00:00:00

  • Mutations within the 5' region of FAS/CD95 gene in nodal diffuse large B-cell lymphoma.

    abstract::CD95 is a cell-surface receptor that mediates apoptosis. A possible association between CD95 mutations and extranodal diffuse large B-cell lymphomas (DLBCL) has been reported. To further elucidate this question, a mutation analysis within the 5' region and exon 9 of CD95 was performed in a series of 66 DLBCL patients,...

    journal_title:Leukemia & lymphoma

    pub_type: 杂志文章


    authors: Scholl V,Stefanoff CG,Hassan R,Spector N,Renault IZ

    更新日期:2007-05-01 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


    authors: Schmid M,Porzsolt F

    更新日期:1995-05-01 00:00:00

  • Transition of polycythemia vera to chronic neutrophilic leukemia.

    abstract::Two cases of polycythemia vera (PV) had transition to a hematological condition compatible with chronic neutrophilic leukemia (CNL) 17 and 8 years after diagnosis, respectively. One patient was treated with carboquone followed by hydroxyurea (HU) and the other with HU during PV phase. On transition, both had neutrophi...

    journal_title:Leukemia & lymphoma

    pub_type: 杂志文章,评审


    authors: Higuchi T,Oba R,Endo M,Harada H,Mori H,Niikura H,Omine M,Fujita K

    更新日期:1999-03-01 00:00:00

  • Rearrangements of the BCL6 gene and chromosome aberrations affecting 3q27 in 54 patients with non-Hodgkin's lymphoma.

    abstract::Chromosome aberrations affecting 3q27 are among the most frequent non-random abnormalities in non-Hodgkin's lymphomas (NHL), especially the diffuse, large cell type. Recently, an association between BCL6 rearrangement and frequent extranodal lesions, rare bone marrow infiltration and a favorable clinical outcome was r...

    journal_title:Leukemia & lymphoma

    pub_type: 杂志文章


    authors: Ohshima A,Miura I,Hashimoto K,Takahashi N,Utsumi S,Nimura T,Saito M,Miki T,Hirosawa S,Miura AB

    更新日期:1997-10-01 00:00:00

  • Prognostic Features in the Myelodysplastic Syndromes: Importance of Morphological Atypia in the Marrow Cell Lineages.

    abstract::In order to clarify the relationship between myelodysplastic morphologic features of marrow cells and prognoses and 1.0 define other prognostic factors, 124 patients with the FAB criteria of myelodysplastic syndrome (MIX) were analysed. These included 57 patients with refractory anemia (RA), 5 RA with ring sideroblast...

    journal_title:Leukemia & lymphoma

    pub_type: 杂志文章


    authors: Takahashi M,Koike T,Kishi K,Moriyama Y,Hayashi S,Shibata A

    更新日期:1990-01-01 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


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

    更新日期:2019-03-01 00:00:00

  • Treatment Options for Hodgkin's Disease During Pregnancy.

    abstract::Treatment results of 47 pregnant women with Hodgkin's disease (HD) are analyzed using data reported in the literature since 1960. Twenty-three of the patients were treated with radiation during pregnancy and 17 of the 23 patients (74%) were reported to be long term disease-free survivors. All of these pregnancies resu...

    journal_title:Leukemia & lymphoma

    pub_type: 杂志文章


    authors: Yahalom J

    更新日期:1990-01-01 00:00:00

  • Emerging role of histone deacetylase inhibitors in the treatment of diffuse large B-cell lymphoma.

    abstract::Although current immunochemotherapy has increased the therapeutic efficacy in diffuse large B-cell lymphoma (DLBCL), there are still some patients who present unfavorable outcomes. Novel effective treatment strategies are needed to improve the prognosis of DLBCL. In this review, we discussed the functional mechanisms ...

    journal_title:Leukemia & lymphoma

    pub_type: 杂志文章


    authors: Wang M,Fang X,Wang X

    更新日期:2020-04-01 00:00:00

  • Central Nervous System (CNS) Involvement in Acute Nonlymphocytic Leukemia (ANLL).

    abstract::The incidence of central nervous system (CNS) involvement and effects of therapy were reviewed in 42 consecutive pediatric patients with acute nonlymphocytic leukemia (ANLL). The morphology of ileukemic cells was considered M1 in 13, M2 in 7, M3 in 5, M4 in 8, and M5 in 9. Two patients with M5 morphology presented wit...

    journal_title:Leukemia & lymphoma

    pub_type: 杂志文章


    authors: Barrios N,Tebbi CK,Freeman AI

    更新日期:1990-01-01 00:00:00

  • Selinexor for advanced hematologic malignancies.

    abstract::Recent measures to classify novel molecular targets with therapeutic potential across multiple hematologic tumors have identified the eukaryotic nuclear exporter, exportin 1 (XPO1), as a promising candidate. Molecular agents termed 'Selective Inhibitors of Nuclear Export' (SINEs) have been developed to selectively inh...

    journal_title:Leukemia & lymphoma

    pub_type: 杂志文章


    authors: Walker JS,Garzon R,Lapalombella R

    更新日期:2020-10-01 00:00:00

  • Target spectrum of the BCR-ABL inhibitors imatinib, nilotinib and dasatinib.

    abstract::Following the initial success of imatinib as frontline therapy for chronic myeloid leukemia (CML), several second-generation therapeutics have been developed with increased potency and the ability to inhibit the majority of imatinib-resistant mutations. Here, we review the current knowledge about the target specificit...

    journal_title:Leukemia & lymphoma

    pub_type: 杂志文章,评审


    authors: Hantschel O,Rix U,Superti-Furga G

    更新日期:2008-04-01 00:00:00

  • Successful treatment with Erwinia L-asparaginase for recurrent natural killer/T cell lymphoma.

    abstract::We describe a patient with natural killer (NK)/T cell lymphoma who relapsed after autologous peripheral blood stem cell transplantation (auto-PBSCT) and was successfully treated with Escherichia coli (E. coli) and Erwinia L-asparaginase. A 38-year-old male patient with ulcerated tumor at the left thigh was diagnosed a...

    journal_title:Leukemia & lymphoma

    pub_type: 杂志文章


    authors: Matsumoto Y,Nomura K,Kanda-Akano Y,Fujita Y,Nakao M,Ueda K,Horiike S,Yokota S,Kusuzaki K,Kitoh T,Watanabe A,Taniwaki M

    更新日期:2003-05-01 00:00:00

  • CLL Trials in the United Kingdom the Medical Research Council CLL Trials 1, 2 and 3.

    abstract::The MRC has conducted randomised trials in CLL sine 1978: CLL 1 (1978-84), 660 patients; CLL 2 (1984-90), 640 patients; CLL 3 (from June 1990), 90 patients. Centralised morphological diagnosis and membrane marker studies have allowed the exclusion of non-CLL disorders. Some of the treatment questions were repeated in ...

    journal_title:Leukemia & lymphoma

    pub_type: 杂志文章


    authors: Catovsky D,Richards S,Fooks J,Hamblin TJ

    更新日期:1991-01-01 00:00:00

  • DNA methylation patterns of adult survivors of adolescent/young adult Hodgkin lymphoma compared to their unaffected monozygotic twin.

    abstract::DNA methylation (DNAm) silences gene expression and may play a role in immune dysregulation that is characteristic of adolescent/young adult Hodgkin lymphoma (AYAHL). We used the Infinium HumanMethylation27 BeadChip to quantify DNAm in blood (N = 9 pairs, mean age 57.4 y) or saliva (N = 36 pairs, mean age 50.0 y) from...

    journal_title:Leukemia & lymphoma

    pub_type: 杂志文章


    authors: Wang J,Van Den Berg D,Hwang AE,Weisenberger D,Triche T,Nathwani BN,Conti DV,Siegmund K,Mack TM,Horvath S,Cozen W

    更新日期:2019-06-01 00:00:00

  • Clinical and epidemiological features of acute lymphoblastic leukemia following a previous malignancy.

    abstract::Secondary malignancies represent a relevant complication of chemotherapy employed for a previous cancer. Acute leukemias represent the most frequent secondary malignancy in the first decade following primary neoplasms; secondary leukemias are generally myeloid and can be preceeded by a myelodysplastic syndrome. The bi...

    journal_title:Leukemia & lymphoma

    pub_type: 杂志文章,评审


    authors: Pagano L,Pulsoni A,Mele L,Leone G

    更新日期:2000-11-01 00:00:00

  • Autologous stem cell transplantations for recurrent adult T cell leukaemia/lymphoma using highly purified CD34+ cells derived from cryopreserved peripheral blood stem cells.

    abstract::We performed double autologous PBSCT in one fulminantly relapsed ATL patient. Cryopreserved PBSCs containing tumour cells were thawed, and CD34+ cells were selected for by immunomagnetic beads, with the aim of decreasing the number of re-infused tumour cells. The patient received 0.72x10(6) and 0.90x10(6) CD34+ cells/...

    journal_title:Leukemia & lymphoma

    pub_type: 杂志文章


    authors: Watanabe J,Kondo H,Hatake K

    更新日期:2001-09-01 00:00:00

  • Fludarabine therapy in Waldenström's macroglobulinemia patients treated previously with 2-chlorodeoxyadenosine.

    abstract::Six patients with Waldenström's macroglobulinemia (WM) resistant to previous 2-chlorodeoxyadenosine (2-CdA) therapy were treated with fludarabine. Both initial and subsequent therapy was administered according to the most widely used protocols. The median number of 2-CdA cycles given to the patients was 3.7 (range 2-5...

    journal_title:Leukemia & lymphoma

    pub_type: 杂志文章


    authors: Lewandowski K,Halaburda K,Hellmann A

    更新日期:2002-02-01 00:00:00

  • Significance of circulating plasma cells in multiple myeloma.

    abstract::The number of circulating plasma cells (CPC) was determined on mononuclear cell preparations after Giemsa (morphology) and light chain staining (immunocytochemistry). Both methods gave reproducible and identical results when CPC were 1% or more. Using this limit, no CPC were observed in MGUS (0/11) and primary amyloid...

    journal_title:Leukemia & lymphoma

    pub_type: 杂志文章


    authors: Zandecki M,Facon T,Preudhomme C,Canis F,Izydorczyk V,Lovi V,Hammad M,Bauters F,Cosson A

    更新日期:1994-08-01 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


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

    更新日期:2009-06-01 00:00:00

  • Novel agents versus chemotherapy as frontline treatment of CLL.

    abstract::Chronic lymphocytic leukemia (CLL) is a neoplastic disorder of mature B lymphocytes. While traditionally treated with combinations of chemoimmunotherapy, the therapeutic options for CLL have expanded in recent years with the emergence of novel oral agents, such as the Bruton tyrosine kinase inhibitor ibrutinib, that a...

    journal_title:Leukemia & lymphoma

    pub_type: 杂志文章,评审


    authors: Piggin A,Bayly E,Tam CS

    更新日期:2017-06-01 00:00:00

  • Overexpression of phosphorylated p27 Kip1 at threonine 187 may predict outcome in aggressive B-cell lymphomas.

    abstract::Phosphorylation of p27(Kip1) at threonine 187 (pThr187-p27(Kip1)) occurs frequently in the development of human tumors, directing protein polyubiquitination and subsequent proteasomal degradation. We investigated the immunoexpression of p27(Kip1) and pThr187-p27(Kip1) in 126 B-cell lymphomas and their relation to prol...

    journal_title:Leukemia & lymphoma

    pub_type: 杂志文章


    authors: Sirinian C,Symeonidis A,Giannakoulas N,Zolota V,Melachrinou M

    更新日期:2011-05-01 00:00:00

  • Ibrutinib in chronic lymphocytic leukemia and B cell malignancies.

    abstract::Recent clinical data suggest remarkable activity of ibrutinib, the first-in-class covalent inhibitor of Bruton's tyrosine kinase (BTK), in chronic lymphocytic leukemia (CLL), as well as excellent activity in other B cell malignancies, including in particular mantle cell lymphoma and Waldenstrom macroglobulinemia. This...

    journal_title:Leukemia & lymphoma

    pub_type: 杂志文章,评审


    authors: Brown JR

    更新日期:2014-02-01 00:00:00

  • Primary and isolated anaplastic large cell lymphoma of the bone marrow.

    abstract::Anaplastic large cell lymphoma (ALCL) is a T-cell lymphoma in which the majority of patients present with advanced stage III or IV disease. Here we report a case of ALCL where bone marrow was the only site of disease, in a 60-year-old man with pyrexia and pancytopenia. The diagnosis of ALCL was made on detection of CD...

    journal_title:Leukemia & lymphoma

    pub_type: 杂志文章


    authors: Gudgin E,Rashbass J,Pulford KJ,Erber WN

    更新日期:2005-03-01 00:00:00

  • The influence of lymphoid reconstitution kinetics on clinical outcomes in allogeneic stem cell transplantation.

    abstract::Lymphoid recovery following myeloablative stem cell transplantation (SCT) displays a logistic pattern of exponential growth followed by a plateau. Within this logistic framework, lymphoid recovery is characterized by the parameters R (slope of ascent), a (time of maximal rate of ascent) and K (plateau), the 'steady-st...

    journal_title:Leukemia & lymphoma

    pub_type: 杂志文章


    authors: Kobulnicky DJ,Sabo RT,Sharma S,Shubar Ali AS,Kobulnicky KM,Roberts CH,Clark WB,Chung HM,McCarty JM,Toor AA

    更新日期:2018-12-01 00:00:00

  • Identification and validation of a prognostic 8-gene signature for acute myeloid leukemia.

    abstract::In the present study, we aimed to identify some genes closely related to AML prognosis and investigate their potential roles. RNA-seq data of AML samples were accessed from the TCGA database and then analyzed in the Wilcox test. AML survival-related genes were selected and an 8-gene signature-based risk score model wa...

    journal_title:Leukemia & lymphoma

    pub_type: 杂志文章


    authors: Zhang Y,Xiao L

    更新日期:2020-08-01 00:00:00

  • Early mortality in children with acute lymphoblastic leukemia in a developing country: the role of malnutrition at diagnosis. A multicenter cohort MIGICCL study.

    abstract::The role of malnutrition at diagnosis as a predictor of early mortality in Mexican leukemia children remains controversial. The objective of present study was to investigate whether malnutrition was a predictor of early mortality during the first year of treatment in Mexican acute lymphoblastic leukemia (ALL) children...

    journal_title:Leukemia & lymphoma

    pub_type: 杂志文章,多中心研究


    authors: Martín-Trejo JA,Núñez-Enríquez JC,Fajardo-Gutiérrez A,Medina-Sansón A,Flores-Lujano J,Jiménez-Hernández E,Amador-Sanchez R,Peñaloza-Gonzalez JG,Alvarez-Rodriguez FJ,Bolea-Murga V,Espinosa-Elizondo RM,de Diego Flores-Chapa J,Pérez

    更新日期:2017-04-01 00:00:00

  • Herbs in hemato-oncological care: an evidence-based review of data on efficacy, safety, and drug interactions.

    abstract::Herbal remedies are clearly a complementary and alternative modality used frequently by patients with hemato-oncological neoplasias during the course of their specific treatment. This review focuses on the potential safety and efficacy of herbs which are either used often or even on a daily basis by patients with hema...

    journal_title:Leukemia & lymphoma

    pub_type: 杂志文章,评审


    authors: Ben-Arye E,Attias S,Tadmor T,Schiff E

    更新日期:2010-08-01 00:00:00

  • Amplification and specific expression of T-bet gene in nasal NK/T-cell lymphoma.

    abstract::To define the specific genetic alterations in nasal natural killer/T-cell lymphoma (N-NK/T-L), the assay of restriction landmark genomic scanning (RLGS), a genome-wide method, was used to investigate a pair of genomic DNA from N-NK/T-L cells and peripheral blood leukocytes of the same patient. The intensified spots in...

    journal_title:Leukemia & lymphoma

    pub_type: 杂志文章


    authors: Ye Y,Li T,Zhang B,Guo Z

    更新日期:2007-01-01 00:00:00

  • Long-term follow-up study on the role of serum CA-125 as a prognostic factor in 221 newly diagnosed patients with Hodgkin's lymphoma.

    abstract::The present study has explored the possible value of sCA-125 as a prognostic factor in Hodgkin's lymphoma (HL). From August 1992 to June 2005 sCA-125 was measured at presentation and at the end of the treatments in 221 newly diagnosed adult patients with HL. In this study 90/221 (41%) patients showed a value greater t...

    journal_title:Leukemia & lymphoma

    pub_type: 杂志文章


    authors: Russo F,Lastoria S,Svanera G,Capobianco G,de Chiara A,Francia Rd,Squame E,de Martinis F,Pinto A

    更新日期:2007-04-01 00:00:00