Calicheamicin-conjugated humanized anti-CD33 monoclonal antibody (gemtuzumab zogamicin, CMA-676) shows cytocidal effect on CD33-positive leukemia cell lines, but is inactive on P-glycoprotein-expressing sublines.


:Calicheamicin-conjugated humanized anti-CD33 mouse monoclonal antibody, CMA-676, has recently been introduced to clinics as a promising drug to treat patients with acute myeloid leukemia (AML) in relapse. However, the mechanism of action of CMA-676 has not been well elucidated. The cytotoxic effect of CMA-676 on HL60, NOMO-1, NB4, NKM-1, K562, Daudi, and the multidrug-resistant sublines, NOMO-1/ADR and NB4/MDR, was investigated by cell cycle distribution and morphology. These studies were done by a video-microscopic system, DNA fragmentation, dye exclusion and 3H-thymidine uptake after analysis of CD33, CD34, P-glycoprotein (P-gp), multidrug resistance (MDR)-associated protein and lung-related protein on these cells. A dose-dependent, selective cytotoxic effect of CMA-676 was observed in cell lines that expressed CD33, and was dependent on the amount of CD33 and the proliferative speed of the cells. Sensitive cells were temporally arrested at the G2/M phase before undergoing morphological changes. CMA-676 is not effective on P-gp-expressing multidrug-resistant sublines compared with parental cell lines. MDR modifiers, MS209 and PSC833, restored the cytotoxic effect of CMA-676 in P-gp-expressing sublines. CMA-676 is a promising agent in the treatment of patients with AML that expresses CD33. The combined use of CMA-676 and MDR modifiers may increase the selective cytotoxic effect in multidrug-resistant AML.






Naito K,Takeshita A,Shigeno K,Nakamura S,Fujisawa S,Shinjo K,Yoshida H,Ohnishi K,Mori M,Terakawa S,Ohno R




Has Abstract


2000-08-01 00:00:00














  • Expression of the CEA gene family members NCA-50/90 and NCA-160 (CD66) in childhood acute lymphoblastic leukemias (ALLs) and in cell lines of B-cell origin.

    abstract::The carcinoembryonic antigen (CEA) and the classical non-specific cross-reacting antigens (NCAs) belong to the CEA gene family which is part of the immunoglobulin superfamily. In normal hematopoiesis, CEA gene family members (CGMs) have only been reported on cells of myeloid and monocytic origin. In the present study,...


    pub_type: 杂志文章


    authors: Hanenberg H,Baumann M,Quentin I,Nagel G,Grosse-Wilde H,von Kleist S,Göbel U,Burdach S,Grunert F

    更新日期:1994-12-01 00:00:00

  • Bone marrow stem cell mobilization in stroke: a 'bonehead' may be good after all!

    abstract::Mobilizing bone cells to the head, astutely referred to as 'bonehead' therapeutic approach, represents a major discipline of regenerative medicine. The last decade has witnessed mounting evidence supporting the capacity of bone marrow (BM)-derived cells to mobilize from BM to peripheral blood (PB), eventually finding ...


    pub_type: 杂志文章,评审


    authors: Borlongan CV

    更新日期:2011-11-01 00:00:00

  • The essential roles of the chemokine SDF-1 and its receptor CXCR4 in human stem cell homing and repopulation of transplanted immune-deficient NOD/SCID and NOD/SCID/B2m(null) mice.

    abstract::Hematopoietic stem cells are identified based on their functional ability to migrate via the blood circulation of transplanted recipients, to home to the host bone marrow and to durably repopulate this organ with high levels of maturing myeloid and lymphoid cells. While a small pool of undifferentiated stem cells with...


    pub_type: 杂志文章,评审


    authors: Lapidot T,Kollet O

    更新日期:2002-10-01 00:00:00

  • Monitoring of WT1 expression in PB and CD34(+) donor chimerism of BM predicts early relapse in AML and MDS patients after hematopoietic cell transplantation with reduced-intensity conditioning.

    abstract::Relapse of malignant disease remains the major complication in patients with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) after hematopoietic cell transplantation (HCT) with reduced-intensity conditioning (RIC). In this study, we investigated the predictive value of disease-specific markers (DSMs), d...


    pub_type: 杂志文章


    authors: Lange T,Hubmann M,Burkhardt R,Franke GN,Cross M,Scholz M,Leiblein S,Al-Ali HK,Edelmann J,Thiery J,Niederwieser D

    更新日期:2011-03-01 00:00:00

  • Flavaglines target primitive leukemia cells and enhance anti-leukemia drug activity.

    abstract::Identification of agents that target human leukemia stem cells is an important consideration for the development of new therapies. The present study demonstrates that rocaglamide and silvestrol, closely related natural products from the flavagline class of compounds, are able to preferentially kill functionally define...


    pub_type: 杂志文章


    authors: Callahan KP,Minhajuddin M,Corbett C,Lagadinou ED,Rossi RM,Grose V,Balys MM,Pan L,Jacob S,Frontier A,Grever MR,Lucas DM,Kinghorn AD,Liesveld JL,Becker MW,Jordan CT

    更新日期:2014-10-01 00:00:00

  • Distinct iron architecture in SF3B1-mutant myelodysplastic syndrome patients is linked to an SLC25A37 splice variant with a retained intron.

    abstract::Perturbation in iron homeostasis is a hallmark of some hematologic diseases. Abnormal sideroblasts with accumulation of iron in the mitochondria are named ring sideroblasts (RS). RS is a cardinal feature of refractory anemia with RS (RARS) and RARS with marked thrombocytosis (RARS/-T). Mutations in SF3B1, a member of ...


    pub_type: 杂志文章


    authors: Visconte V,Avishai N,Mahfouz R,Tabarroki A,Cowen J,Sharghi-Moshtaghin R,Hitomi M,Rogers HJ,Hasrouni E,Phillips J,Sekeres MA,Heuer AH,Saunthararajah Y,Barnard J,Tiu RV

    更新日期:2015-01-01 00:00:00

  • Phase 1/2 study of weekly carfilzomib, cyclophosphamide, dexamethasone in newly diagnosed transplant-ineligible myeloma.

    abstract::This multicentre, open-label phase 1/2 trial determined safety and efficacy of weekly carfilzomib plus cyclophosphamide-dexamethasone (wKCyd) in newly diagnosed multiple myeloma (NDMM) patients aged ⩾65 years or transplant ineligible. Patients received wKCyd for up to nine 28-day cycles, followed by maintenance with c...


    pub_type: 杂志文章,多中心研究


    authors: Bringhen S,D'Agostino M,De Paoli L,Montefusco V,Liberati AM,Galieni P,Grammatico S,Muccio VE,Esma F,De Angelis C,Musto P,Ballanti S,Offidani M,Petrucci MT,Gaidano G,Corradini P,Palumbo A,Sonneveld P,Boccadoro M

    更新日期:2018-04-01 00:00:00

  • Targeting MYC in multiple myeloma.

    abstract::Multiple myeloma (MM) is a plasma cell tumor marked by clonal evolution and preceded by a premalignant stage, which progresses via molecular pathway deregulation, including MYC activation. This activation relates to translocation or gain of the MYC locus and deregulation of upstream pathways such as IRF4, DIS3/LIN28B/...


    pub_type: 杂志文章,评审


    authors: Jovanović KK,Roche-Lestienne C,Ghobrial IM,Facon T,Quesnel B,Manier S

    更新日期:2018-06-01 00:00:00

  • B-cell maturation antigen (BCMA) in multiple myeloma: rationale for targeting and current therapeutic approaches.

    abstract::Despite considerable advances in the treatment of multiple myeloma (MM) in the last decade, a substantial proportion of patients do not respond to current therapies or have a short duration of response. Furthermore, these treatments can have notable morbidity and are not uniformly tolerated in all patients. As there i...


    pub_type: 杂志文章,评审


    authors: Shah N,Chari A,Scott E,Mezzi K,Usmani SZ

    更新日期:2020-04-01 00:00:00

  • Heterogeneity of VH-JH gene rearrangement patterns: an insight into the biology of B cell precursor ALL.

    abstract::Oligoclonal B cell proliferation, as defined by the presence of more than one leukemic clone, has been detected in approximately 20% to 30% of patients with acute lymphoblastic leukemia (ALL) using PCR or Southern blotting. An accurate assessment of these populations is required to avoid false negative measurements of...


    pub_type: 杂志文章


    authors: Moreira I,Papaioannou M,Mortuza FY,Gameiro P,Palmisano GL,Harrison CJ,Prentice HG,Mehta AB,Hoffbrand AV,Foroni L

    更新日期:2001-10-01 00:00:00

  • Deletion analysis of chromosome 13q14.3 and characterisation of an alternative splice form of LEU1 in B cell chronic lymphocytic leukemia.

    abstract::Heterozygous and homozygous deletions of chromosome 13q14.3 are found in 50% of patients with B cell CLL, suggesting the presence of one or more tumour suppressor genes within the deleted region. To identify candidate genes from the region, we constructed a map of 13q14.3 using a combination of genomic and cDNA librar...


    pub_type: 杂志文章


    authors: Rowntree C,Duke V,Panayiotidis P,Kotsi P,Palmisano GL,Hoffbrand AV,Foroni L

    更新日期:2002-07-01 00:00:00

  • CD200 expression suppresses natural killer cell function and directly inhibits patient anti-tumor response in acute myeloid leukemia.

    abstract::Upregulation of the immunosuppressive cell surface glycoprotein, CD200, is a common feature of acute myeloid leukemia (AML) and is associated with poor patient outcome. We investigated whether CD200 overexpression on AML cells could specifically compromise patient natural killer (NK) cell anti-tumor responses. We foun...


    pub_type: 杂志文章


    authors: Coles SJ,Wang EC,Man S,Hills RK,Burnett AK,Tonks A,Darley RL

    更新日期:2011-05-01 00:00:00

  • Loss of bone mass and vitamin D deficiency after hematopoietic stem cell transplantation: standard prophylactic measures fail to prevent osteoporosis.

    abstract::Bone mineral density (BMD) and biochemical markers of bone metabolism were analyzed in 67 adults with ALL (n = 27), AML (n = 14), MDS (n = 6) and CML (n = 20) before and after allogeneic stem cell transplantation (SCT). Median age was 36 years (17-56). Twenty-six out of 53 patients (49%) had osteopenia and osteoporosi...


    pub_type: 临床试验,杂志文章


    authors: Massenkeil G,Fiene C,Rosen O,Michael R,Reisinger W,Arnold R

    更新日期:2001-11-01 00:00:00

  • Different isoforms of the B-cell mutator activation-induced cytidine deaminase are aberrantly expressed in BCR-ABL1-positive acute lymphoblastic leukemia patients.

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    pub_type: 杂志文章


    authors: Iacobucci I,Lonetti A,Messa F,Ferrari A,Cilloni D,Soverini S,Paoloni F,Arruga F,Ottaviani E,Chiaretti S,Messina M,Vignetti M,Papayannidis C,Vitale A,Pane F,Piccaluga PP,Paolini S,Berton G,Baruzzi A,Saglio G,Baccar

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  • High leucovorin doses during high-dose methotrexate treatment may reduce the cure rate in childhood acute lymphoblastic leukemia.

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    pub_type: 杂志文章


    authors: Skärby TV,Anderson H,Heldrup J,Kanerva JA,Seidel H,Schmiegelow K,Nordic Society of Paediatric Haematology and Oncology (NOPHO).

    更新日期:2006-11-01 00:00:00

  • Natural killer-cell malignancies: diagnosis and treatment.

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    pub_type: 杂志文章,评审


    authors: Kwong YL

    更新日期:2005-12-01 00:00:00

  • IL-2 inhibits proliferation of K562 cells and reduces accumulation of bcr/abl mRNA and oncoprotein.

    abstract::Cell lines of myeloid origin have been shown to express interleukin-2 receptors (IL-2R). Here, we demonstrate the expression of IL-2R alpha and IL-R beta on the CML blast cell line K562 by FACS analysis and cross-linking assay. Furthermore, we examined the effect of IL-2 on leukemic progenitor growth, employing K562 a...


    pub_type: 杂志文章


    authors: Dilloo D,Hanenberg H,Lion T,Burdach S

    更新日期:1995-03-01 00:00:00

  • Physical association of the patient-specific GATA1 mutants with RUNX1 in acute megakaryoblastic leukemia accompanying Down syndrome.

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    pub_type: 杂志文章


    authors: Xu G,Kanezaki R,Toki T,Watanabe S,Takahashi Y,Terui K,Kitabayashi I,Ito E

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  • Establishment and characterization of a new human megakaryoblastic cell line (SET-2) that spontaneously matures to megakaryocytes and produces platelet-like particles.

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    pub_type: 杂志文章


    authors: Uozumi K,Otsuka M,Ohno N,Moriyama T,Suzuki S,Shimotakahara S,Matsumura I,Hanada S,Arima T

    更新日期:2000-01-01 00:00:00

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    pub_type: 杂志文章


    authors: Secker-Walker LM,Moorman AV,Bain BJ,Mehta AB

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    pub_type: 杂志文章


    authors: Sasaki H,Kajigaya Y,Hirabayashi Y,Funabiki T,Inoue T,Yokota T,Ikuta K,Arai K,Matsuyama S

    更新日期:1991-05-01 00:00:00

  • Leukemic dendritic cells generated in the presence of FLT3 ligand have the capacity to stimulate an autologous leukemia-specific cytotoxic T cell response from patients with acute myeloid leukemia.

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    pub_type: 杂志文章


    authors: Woiciechowsky A,Regn S,Kolb HJ,Roskrow M

    更新日期:2001-02-01 00:00:00

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    pub_type: 杂志文章


    authors: Guyotat D,Campos L,Shi ZH,Charrin C,Treille D,Magaud JP,Fiere D

    更新日期:1990-09-01 00:00:00

  • Outcome of older (≥70 years) APL patients frontline treated with or without arsenic trioxide-an International Collaborative Study.

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    pub_type: 杂志文章,多中心研究


    authors: Kayser S,Rahmé R,Martínez-Cuadrón D,Ghiaur G,Thomas X,Sobas M,Guerci-Bresler A,Garrido A,Pigneux A,Gil C,Raffoux E,Tormo M,Vey N,de la Serna J,Salamero O,Lengfelder E,Levis MJ,Fenaux P,Sanz MA,Platzbecker U,Schlen

    更新日期:2020-09-01 00:00:00

  • Clinical and pharmacokinetic studies of all-trans-retinoic acid in pediatric patients with cancer.

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    pub_type: 临床试验,杂志文章


    authors: Adamson PC

    更新日期:1994-01-01 00:00:00

  • Prevalence and clinicopathologic correlates of JAK2 exon 12 mutations in JAK2V617F-negative polycythemia vera.

    abstract::After accounting for misdiagnosis and treatment effect, allele-specific (AS)-PCR detects the JAK2V617F mutation in >95% of polycythemia vera (PV) patients. Using database inquiry, we identified 6 of a total 220 cases with PV that were JAK2V617F-negative (prevalence=3%). Of these, five cases ( approximately 80%) were f...


    pub_type: 杂志文章


    authors: Pardanani A,Lasho TL,Finke C,Hanson CA,Tefferi A

    更新日期:2007-09-01 00:00:00

  • Continued improvement in survival in multiple myeloma: changes in early mortality and outcomes in older patients.

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    pub_type: 杂志文章


    authors: Kumar SK,Dispenzieri A,Lacy MQ,Gertz MA,Buadi FK,Pandey S,Kapoor P,Dingli D,Hayman SR,Leung N,Lust J,McCurdy A,Russell SJ,Zeldenrust SR,Kyle RA,Rajkumar SV

    更新日期:2014-05-01 00:00:00

  • A phase II study of cladribine treatment for fludarabine refractory B cell chronic lymphocytic leukemia: results from CALGB Study 9211.

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    pub_type: 临床试验,杂志文章,多中心研究


    authors: Byrd JC,Peterson B,Piro L,Saven A,Vardiman JW,Larson RA,Schiffer C

    更新日期:2003-02-01 00:00:00

  • Cyclooxygenase-1, but not -2, is upregulated in NB4 leukemic cells and human primary promyelocytic blasts during differentiation.

    abstract::Cyclooxygenase (COX)-1 or -2 and specific prostaglandin (PG) synthases catalyze the formation of various PGs. We investigated the expression and activity of COX-1 and -2 during granulocyte-oriented maturation induced by all-trans-retinoic acid (ATRA) of NB4 cells, originated from a human acute promyelocytic leukemia (...


    pub_type: 杂志文章


    authors: Rocca B,Morosetti R,Habib A,Maggiano N,Zassadowski F,Ciabattoni G,Chomienne C,Papp B,Ranelletti FO

    更新日期:2004-08-01 00:00:00

  • Treatment results of three consecutive Brazilian cooperative childhood ALL protocols: GBTLI-80, GBTLI-82 and -85. ALL Brazilian Group.

    abstract::The Brazilian Cooperative Group for Treatment of Childhood Acute Lymphocytic Leukemia (GBTLI) has started clinical activities trials in 1980. Three consecutive multicenter studies in children with unprevious treated ALL have been completed including 994 patients. The first GBTLI-80 accrued 203 children from 1980 to 19...


    pub_type: 临床试验,杂志文章,多中心研究,随机对照试验


    authors: Brandalise S,Odone V,Pereira W,Andrea M,Zanichelli M,Aranega V

    更新日期:1993-08-01 00:00:00