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  • American Society of Hematology  (37)
  • 2005-2009  (37)
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  • American Society of Hematology  (37)
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  • 2005-2009  (37)
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Subjects(RVK)
  • 1
    Online Resource
    Online Resource
    Comparison of the Effects on Reversal of Multi-Drug Resistance of 5-Bromotetrandrine and Tetrandrine in K562/A02 Cell Line in Vivo and in Vitro
    American Society of Hematology ; 2008
    In:  Blood Vol. 112, No. 11 ( 2008-11-16), p. 5059-5059
    Details
    In: Blood, American Society of Hematology, Vol. 112, No. 11 ( 2008-11-16), p. 5059-5059
    Abstract: Objective This study was to compare the reversal effect of 5-bromotetrandrine (BrTet) with Tetrandrine (Tet) when combined with ADM on multidrug resistance cell line K562/A02 and to investigate the reversal mechanism of this new derivative. Methods The protein levels of P-glycoprotein (P-gp) were detected by fluorospectrophotometry and Western blot. The mRNA levels of P-gp were determined by RT-PCR. The in vivo effect of Tet was investigated using nude mice grafted with sensitive human leukemia cell line K562 and MDR cell line K562/A02. Results Flow cytometry assay showed that 1.0 μMol/L BrTet significantly increased the apoptosis percentage. BrTet also enhanced the intracellular accumulation of ADM in K562/A02 cells and its potency was greater than that of Tet at the same concentrations. BrTet inhibited the overexpression of P-gp and down regulated MDR1 mRNA expression in K562/A02 cells in a dose-dependent manner. In nude mice bearing K562 xenografts on the left flank and K562/A02 xenografts on the right flank, i.p. injection of 10 mg/kg BrTet significantly enhanced the antitumor activity of ADM against K562/A02 xenografts with inhibitory rates of 26.1%, while ADM alone inhibited the growth of KBv200 xenografts by only 5.8%. Conclusion BrTet showed significant MDR reversal activity in vitro and in vivo. Its activity may be related to the inhibition of P-gp overexpression and the increase in intracellular accumulation of anticancer drugs, which lead to more K562/A02 cells apoptosis.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    URL: Article
    DOI: 10.1182/blood.V112.11.5059.5059
    RVK:
    XA 33000
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2008
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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  • 2
    Online Resource
    Online Resource
    Mechanism Research of Reversal of Multidrug Resistance by the Application of 5-Bromotetrandrine and Magnetic Nanoparticle of Fe3O4 Combined with Daunorubicin in a Human-Nude Mice Xenograft Model
    American Society of Hematology ; 2008
    In:  Blood Vol. 112, No. 11 ( 2008-11-16), p. 5058-5058
    Details
    In: Blood, American Society of Hematology, Vol. 112, No. 11 ( 2008-11-16), p. 5058-5058
    Abstract: Objective: To establish the xenograft leukemia model with stable multiple drug resistance in nude mice; to investigate the reversal effect of 5-Bromotetrandrine and Magnetic nanoparticle of Fe3O4 combined with DNR in vivo and to search for the possible reversal mechanisms. Methods: K562 and K562/A02 cells were respectively inoculated subcutaneously into back of athymic nude mice (1×107 cells/each) to establish the xenograft models. The tumor formation was evaluated by animal ultrasonic inspection. Tumors-bearing nude mice were assigned randomly to five groups which were treated with NS (A group); DNR 1mg/kg (B group); nanoparticle of Fe3O4 combined with DNR 0.63mg/kg(C group): 5-BrTet 2.5mg/kg combined with DNR(D group); 5-Bromotetrandrine 2.5mg/kg and Magnetic nanoparticle of Fe3O4 combined with DNR 0.63mg/kg(E group) respectively. The incidence of tumor formation, growth characteristics, weight and volume of tumor were observed. The histopathologic examination of tumors and organs were detected. For resistant tumors, the protein levels of P-glycoprotein (P-gp) were detected by Western blot. Results: The tumor incidence was 100% in the nude mice inoculated with either K562 or K562/A02 cells. In 6 to 9 days,the tumors reached a volume of more than 1 00 mm3. In vivo, MTT assay showed K562/A02 tumor maintained the drug resistance. For K562 cells xenograft tumors, there were no apparent differences in tumor suppression effect between the B AC AD AE group. For K562/A02 cells xenograft tumors, 5-BrTet and Magnetic nanoparticle of Fe3O4 combined with DNR significantly suppressed growth of tumor: the inhibition rate was 62.76% while DNR alone be used, the inhibition rate was 3.68%. Pathologic examination of resistant tumors showed the tumors necrosis obviously in E group. Application of 5-BrTet and Magnetic nanoparticle of Fe3O4 inhibited the overexpression of P-gp. Conclusion: The xenograft leukemia nude mice model was maintain the multiple drug resistance. 5-Bromotetrandrine and Magnetic nanoparticle of Fe3O4 combined with DNR had a significant tumor-suppressing effect on MDR leukemia cells xenograft model.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    URL: Article
    DOI: 10.1182/blood.V112.11.5058.5058
    RVK:
    XA 33000
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2008
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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  • 3
    Online Resource
    Online Resource
    Magnetic Nanoparticle of Fe3O4 Loaded with Daunorubicin Reverse Leukemia Multidrug Resistance in Vivo
    American Society of Hematology ; 2008
    In:  Blood Vol. 112, No. 11 ( 2008-11-16), p. 5062-5062
    Details
    In: Blood, American Society of Hematology, Vol. 112, No. 11 ( 2008-11-16), p. 5062-5062
    Abstract: Object: To the effect of Fe3O4-magnetic nanoparticle loaded with DNR on In order to study the multidrug-resistant reversal effect of Fe3O4-magnetic nanoparticle loaded with DNR in vivo. Methods: K562-n,a leukemia cell line with high tumorigenicity in nude mice and its multidrug-resistant counterpart K562-n/VCR cells were inoculated subcutaneously into each groins of nude mice (5×106 cells/each) to establish a human leukemia xenograft model. The mice were randomly divided into group A receiving normal saline, group B receiving anti-tumor drugs daunorubicin (DNR), group C receiving Fe3O4-magnetic nanoparticle, group D receiving Fe3O4-magnetic nanoparticle loaded with DNR, and group E receiving Fe3O4-magnetic nanoparticle containing DNR with a magnetic field built on the surface of tumor tissues. After 20 days treatments, mice were killed and tumor tissues were isolated for pathological observation. The volume and weight of tumors were measured, then tumor suppression rate was calculated. The side effects of DNR loaded Fe3O4-magnetic nanoparticle were also evaluated. Results: The results showed that DNR loaded Fe3O4-magnetic nanoparticle can significantly suppress the growth of K562-n/VCR tumor in vivo, DNR alone can greatly suppress the growth of K562-n, Fe3O4-magnetic nanoparticle loaded with DNR can not further inhibit the K562-n tumor. Conclusion: In conclusion, Fe3O4-magnetic nanoparticle loaded with DNR can reverse the leukemia multidrug resistance in vivo.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    URL: Article
    DOI: 10.1182/blood.V112.11.5062.5062
    RVK:
    XA 33000
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2008
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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  • 4
    Online Resource
    Online Resource
    Effect of Tetrandrine and Toremifene on the Reversion of Multidrug Resistance of K562/A02 Cell Line
    American Society of Hematology ; 2008
    In:  Blood Vol. 112, No. 11 ( 2008-11-16), p. 5063-5063
    Details
    In: Blood, American Society of Hematology, Vol. 112, No. 11 ( 2008-11-16), p. 5063-5063
    Abstract: Objective: To study the reversal effect of Tetrandrine(Tet) and the estrogen-receptor inhibitor,toremifene(Tor),on multidrug resistance cell line K562/A02 and to investigate the reversal mechanism of this combination. Methods: ADM accumulation and the apoptosis percentage of K562 and K562/A02 cells were analyzed by fluorospectrophotometry, respectively. The protein levels of P-glycoprotein (P-gp) were detected by fluorospectrophotometry. The mRNA levels of mdr1 and Survivin were determined by RT-PCR. Results: The IC50 of ADM for K562/A02 and K562 cells were 57.43±4.55mg/L and 1.16±0.05mg/L respectively. Pretreating K562/A02 cells with toremifene(2.5μmol/L) or Tet(1μmol/L) for 72 hours partially restored the sensitivity of K562/A02 cells to ADM (IC50 were 20.74±1.62mg/L and 14.12±1.20mg/L respectively) but had no effect on K562 cells; IC50 of combined tetrandrine and toremifene was 9.14±1.03mg/L;K562/A02 showed apoptotic characteristics after treated with tetrandrine, toremifene (alone or combination);tetrandrine and toremifene (alone or combination) elevated the intracellular ADM accumulation in K562/A02; P-gp, mdr1 and Survivin mRNA were down regulated. Conclusion: Tetrandrine, toremifene (alone or combination) showed significant MDR reversal activity in vitro The reversal activity may be related to the inhibition of P-gp overexpression and down regulation the expression of mdr1 and Survivin mRNA to increase the intracellular accumulation of anticancer drugs, which lead to more K562/A02 cells apoptosis; Multidrug resistance (MDR) can be partially reversed by Tet or Tor of which the combination shows a great synergistic reversal effect.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    URL: Article
    DOI: 10.1182/blood.V112.11.5063.5063
    RVK:
    XA 33000
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2008
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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  • 5
    Online Resource
    Online Resource
    Mechanism Research of Reversal in Multidrug Resistance by Magnetic Nanoparticle Fe3O4 Syndesis with 5-Bromotetrandrine and Daunomycin
    American Society of Hematology ; 2008
    In:  Blood Vol. 112, No. 11 ( 2008-11-16), p. 5064-5064
    Details
    In: Blood, American Society of Hematology, Vol. 112, No. 11 ( 2008-11-16), p. 5064-5064
    Abstract: Objective To evaluate the MDR reversal activity of magnetic nanoparticle Fe3O4 (Nano-Fe3O4) and 5-bromotetrandrine (BrTet) on multidrug resistance cell line K562/A02 solitarily or symphysially, and to investigate the reversal mechanism of this coopration. Methods The proliferation of K562 and K562/A02 cells which were cultured with daunomycin (DNR) alone or in combination with Nano-Fe3O4, BrTet or both for 48h were evaluated by MTT assay. DNR accumulation and P-gp of K562 and K562/A02 were analyzed by fluorospectrophotometry. Results The IC50 of DNR for K562 and K562/A02 cells were 2.74±0.19μM and 32.33±8.40μM, respectively; but the sensitivity of K562/A02 cells to DNR was partially restored after culturing with Nano-Fe3O4, BrTet solitarily and symphysially (the IC50 were 7.04±0.85μM, 4.25±2.16μM, 1.80±0.30μM; the FR were 4.32, 7.61, 17.96, respectively), but had no effects on K562 cell lines. The differences had statistical significance. Flow cytometry assay showed that Nano-Fe3O4 and BrTet increased the DNR accumulation in K562/A02 cells, especially in the group of synergia of these two agents. The mean fluorescence intensity of endocellular DNR increased from 2614 pretreated with DNR only to 4783 incubated with these two reversal reagents, while the values were 3364, 4077 for incubating with Nano-Fe3O4 and BrTet respectively. P-gp were down regulated through pretreating with Nano-Fe3O4, BrTet alone and symphysially in K562/A02 cells by fluorospectrophotometry assay. Conclusion Nano-Fe3O4 and BrTet synergisticly showed significant MDR reversal activity in vitro. The reversal activity may be related to the inhibition of P-gp overexpression and the increasing of the anticancer drug accumulation intracelluarly.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    URL: Article
    DOI: 10.1182/blood.V112.11.5064.5064
    RVK:
    XA 33000
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2008
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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  • 6
    Online Resource
    Online Resource
    Research of Apoptosis Induction by the Application of Magnetic Nanoparticle of Fe3O4 Loaded with Daunorubicin and 5-Bromotetrandrine in K562/A02 Leukemic Cells
    American Society of Hematology ; 2008
    In:  Blood Vol. 112, No. 11 ( 2008-11-16), p. 5060-5060
    Details
    In: Blood, American Society of Hematology, Vol. 112, No. 11 ( 2008-11-16), p. 5060-5060
    Abstract: Objective: To observe the apoptosis of K562/A02 cells induced by application of Fe3O4-Magnetic Nanoparticle (Fe3O4-MNPs) loaded with Daunorubicin(DNR) and 5-Bromotetrandrine (BrTet) and to explore its possible molecular mechanism. Methods: We detected the apoptosis of K562/A02 cells after treatment with Fe3O4-MNPs and BrTet with DNR alone or their combination by flow cytometry(FCM),Wright staining and DNA ladder. The expression of Bax and Bcl-2 protein was measured by Western blot. Results: The result showed apoptotic characteristics after treated with this composite for 48 hours. Flow cytometry assay showed the percentage of apoptotic cells which were treated with Fe3O4-MNPs and BrTet with DNR alone or their combination for 48 hours increased from (7.9%±0.35)% to (15.5%±0.87)%, (19.7%±1.04)% and(40.8%±1.74)%, (P & lt;0.05. After treated with this composite, the typical apoptotic morphological features appeared: condensation of cells and nuclear, disintegration of nuclear chromatin, and apoptotic body could be observed under microscope; DNA agarose gel electrophoresis showed ladder bands; the expression level of Bax protein increased (P & lt; 0.01) and Bcl-2 protein decreased markedly (P & lt; 0.01). Conclusion: Our results suggest that Fe3O4-MNPs or BrTet with DNR induces apoptosis in K562/ADM cells, and when used together,they have distinct synergism. The up-regulation of Bax protein and the down-regulation of Bcl-2 protein may play important roles.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    URL: Article
    DOI: 10.1182/blood.V112.11.5060.5060
    RVK:
    XA 33000
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2008
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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  • 7
    Online Resource
    Online Resource
    Molecular Biological Mechanisms of Cyclosporine a, Tetrandrine and Their Combination on the Reversion of Multidrug Resistance in Leukemia Cell Line
    American Society of Hematology ; 2008
    In:  Blood Vol. 112, No. 11 ( 2008-11-16), p. 5065-5065
    Details
    In: Blood, American Society of Hematology, Vol. 112, No. 11 ( 2008-11-16), p. 5065-5065
    Abstract: Objective Previous researches confirmed that multidrugresistance(MDR) plays an important role in the failure of chemotherapy on malignant tumors. This study was to investigate the molecular biological mechanisms of cyclosporine A(CsA), tetrandrine(Tet) and their combination on multidrug resistance cell line K562/A02. Methods K562/A02 cells were treated with cyclosporine A and (or) tetrandrine. The intracellular DNR concentration and the expression of P-glyco-protein (P-gp) were observed by flow cytometry (FCM) assay. The mRNA expression of mdr-1 was measured by fluorescent semi-quantitative reverse transcriptase polymerase chain reaction(RT-PCR). Resulds CsA and Tet (alone or combination) elevated the intracellular DNR concentration in K562/A02 cells(the fluorescence intensity of intracellelar DNR in K562/A02 cells was 60%,65% and 98% respectively of that in K562 cells); The fluorescence intensity of P-gp in K562 and K562/A02 cells was 0.5% and 97.97%. The P-gp expression was down after treated with CsA,Tet and both(75.32%,76.86% and 48.61%); mdr1 mRNA was also down regulated, and the effect of their combination was greater. Conclusion Multidrug resistance (MDR) can be partially reversed by CsA or Tet, the combination of both drugs shows a great synergistic reversal effect.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    URL: Article
    DOI: 10.1182/blood.V112.11.5065.5065
    RVK:
    XA 33000
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2008
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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  • 8
    Online Resource
    Online Resource
    Variation of p21, P-Gp Expression in K562/A02 Cell Line with Tetrandrine
    American Society of Hematology ; 2008
    In:  Blood Vol. 112, No. 11 ( 2008-11-16), p. 5066-5066
    Details
    In: Blood, American Society of Hematology, Vol. 112, No. 11 ( 2008-11-16), p. 5066-5066
    Abstract: Object: To study the variation of p21, P-gp expression in reversion of multidrug resistance of K562/A02 leukemic line with different concentration of tetrandrine(TET), to provide new theoretic evidence for the clinical application of TET. Methods: The IC50 (the concentration causing 50% inhibition of cell growth) of DNR was analyzed by MTT method; The Expressions of p21 were assayed by westernblot; The Expressions of P-gp were assayed by FCM; The expressions of mdr1 were assayed by RT-PCR; The variation of p21 was accentuation with the accrescence concentration of TET(P & lt;0.05). Results: The variation of p21 protein in K562/A02 cells was accentuation with the accrescence concentration of TET(p & lt;0.05), Mdr1 mRNA was lowly displayed in K562 cells and highly displayed in K562/A02 cells(p & lt;0.01), the variation of mdr1 was attenuation with the accrescence concentration of TET(p & lt;0.05); P-gp was lowly displayed in K562 cells and highly displayed in K562/A02 cells(p & lt;0.01), the variation of P-gp was attenuation with the accrescence concentration of TET(p & lt;0.05). Conclusion: TET may reverse multidrug resistance of K562/A02 cells by the regulation of p21,P-gp and mdr1.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    URL: Article
    DOI: 10.1182/blood.V112.11.5066.5066
    RVK:
    XA 33000
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2008
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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  • 9
    Online Resource
    Online Resource
    Mechanism Research of Magnetic Nanoparticle Fe3O4 and 5-Bromotetrandrine On Reversal of Multidrug Resistance in K562/A02 Leukemic Cells.
    American Society of Hematology ; 2009
    In:  Blood Vol. 114, No. 22 ( 2009-11-20), p. 4827-4827
    Details
    In: Blood, American Society of Hematology, Vol. 114, No. 22 ( 2009-11-20), p. 4827-4827
    Abstract: Abstract 4827 Purpose The present study aimed to research the machenism of magnetic nanoparticles Fe3O4 (Fe3O4-MNPs) and 5-bromotetrandrine (BrTet) on multidrug resistance cell line K562/A02 solitarily or symphysially. Mothed The proliferation of K562 and K562/A02 cells, and the cytotoxicity of PMBCs which were cultured with daunomycin (DNR) alone or in combination with Fe3O4-MNPs (0.1, V/V), BrTet (0.5μM) or both for 48 h, were evaluated by MTT assay. DNR accumulation of K562, K562/A02 cells and PMBCs were analyzed by fluorospectrophotometry after incubated with 2μM DNR in the absence or presence with Fe3O4-MNPs (0.1 V/V), BrTet (0.5μM) or both for 48 h. Real time–PCR analyses and western blotting were performed to examine the mRNA and proteins level, respectively. Result The results showed that the combination of Fe3O4-MNPs and BrTet with effective concentration could exaggerate cytotoxicity against MDR cell line K562/A02 significantly. Flow cytometry assay showed that 0.5μM BrTet in combination with Fe3O4-MNPs (0.1, V/V) significantly enhanced the intracellular accumulation of DNR in K562/A02 cells and its potency was greater than that of BrTet or Fe3O4-MNPs alone at the same concentrations. While both Fe3O4-MNPs and BrTet in company with DNR did not increase the cytotoxicity to PMBCs. Both BrTet and Fe3O4-MNPs inhibited the overexpression of MRP1, MRP2, MRP4 and MRP5, and down regulated, mrps mRNA expression in K562/A02 cells to some extent. Conclusion We propose that Fe3O4-MNPs loaded with DNR and BrTet probably have synergetic effect on reversal in multidrug resistance. However, this combination shows less cytotoxicity to normal cells and reveals better target. The results may provide evidence for clinic application of them as reversal agents of drug resistance. Disclosures No relevant conflicts of interest to declare.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    URL: Article
    DOI: 10.1182/blood.V114.22.4827.4827
    RVK:
    XA 33000
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2009
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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  • 10
    Online Resource
    Online Resource
    Daunorubicin Loaded Magnetic Nanoparticles of Fe3O4 Greatly Enhance the Responses to Chemotherapy and Induce Apoptosis of Multidrug-Resistant K562 Cells in a Human-Nude Mice Xenograft Leukemia Model
    American Society of Hematology ; 2008
    In:  Blood Vol. 112, No. 11 ( 2008-11-16), p. 5038-5038
    Details
    In: Blood, American Society of Hematology, Vol. 112, No. 11 ( 2008-11-16), p. 5038-5038
    Abstract: Object: To the effect of Fe3O4-magnetic nanoparticle loaded with DNR on multidrugresistant K562 cells in vivo. Methods: K562-n and its MDR counterpart K562-n/VCR cell were inoculated subcutaneously into both sides of the back of nude mice (5×106 cells/each) to establish a human leukemia xenograft model. The mice were randomly divided into group A receiving normal saline every other day for 20days, group B receiving DNR every other day for 20days, group C receiving Fe3O4-magnetic nanoparticle every other day for 20days, group D receiving Fe3O4-magnetic nanoparticle loaded with DNR every other day for 20days, and group E receiving Fe3O4-magnetic nanoparticle containing DNR every other day for 20days with a magnetic field built on the surface of the tumor tissue. The tumor volume was measured on the day 1, 5, 9, 13, 17 and 21d after the first treatment. Tumor tissues were isolated for examination of the expression of mdr-1, bcl-2, bax and caspase-3 by reverse transcription polymerase chain reaction and Western blotting. Results: For K562-n/VCR tumor, the tumor volume was markedly lower in groups D and E than in groups A, B and C (group D or E vs group A, B or C, P & lt; 0.05). The transcription of mdr-1 and Bcl-2 gene was significantly lower in groups D and E than in groups A, B and C (group D or E vs group A, B or C, P & lt; 0.05). So did the protein expression of Bcl-2. However, there were no differences among these groups about the protein expression of P-gp. The protein and mRNA expressions of Bax and Caspase-3 in groups D and E were increased significantly compared with groups A, B and C (group D or E vs group A, B or C, P & lt; 0.05). The tumor volume of K562-n was markedly lower in groups C, D and E than in groups A and B (group C, D or E vs group A or B, P & lt; 0.05). Conclusion: In conclusion, DNR loaded Fe3O4-magnetic nanoparticles can suppress the growth and induce apoptosis further on the MDR K562-n/VCR tumor in vivo compared to DNR alone but not on the K562-n tumor. The external magnetic field failed to improve the antitumor effect.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    URL: Article
    DOI: 10.1182/blood.V112.11.5038.5038
    RVK:
    XA 33000
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2008
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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