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Wednesday, August 27, 2008
 Latest
Acute Myeloid Leukemia News Headlines
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Acute Myeloid Leukemia News Headlines
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All Recent Acute Myeloid Leukemia News Headlines |
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Moz/tif2-induced acute myeloid leukaemia in transgenic fish
The inv(8)(p11q13) chromosomal abnormality, described in acute myeloid leukaemias (AML), fuses the histone acetyl-transferase (HAT) MYST3 (MOZ) gene with another HAT gene, NCOA2 (TIF2). We generated a transgenic zebrafish in which the MYST3/NCOA2 fusion gene was expressed under control of the spi1 promoter. An AML developed in 2 of 180 MYST3/NCOA2-EGFP-expressing embryos, 14 and 26 months after injection of the fusion gene in a one-cell embryo, respectively. This leukaemia was characterised by an extensive invasion of kidneys by myeloid blast cells. This model, which is the first zebrafish model of AML, demonstrates the oncogenic potency of MYST3/NCOA2 fusion gene. (Source: British Journal of Haematology)...
POSTED 08/21/2008 at 11:00 PM --
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Myelodysplastic syndrome
Abstract Pediatric myelodysplastic syndrome (MDS), though rare, constitutes a distinct entity quite different from adult MDS. They
have unique clinical features, aggressive clinical course with an overall mean survival of only 9.9 months. A pediatric approach
to the WHO classification has become necessary since the WHO classification of MDS has failed to address the uniqueness of
pediatric MDS. A new prognostic system also needs to be evolved since the international prognostic system has limited prognostic
impact in children. Intensive chemotherapy such as the one used in de novo-acute myeloid leukemia (AML) leads to complete
remission in some children and this may be the treatment of choice in pediatric MDS.
Content Type Journal ArticleCategory Symposium on Advances in HematologyDOI 10.1007/s12098-008-0138-yAuthors
V. Tilak, Banaras Hindu University Department of Pathology, Institute of Medical Sciences Varanasi IndiaD. D. Sookmane, Banaras Hindu University Department of Pathology, Institute of Medical Sciences Varanasi IndiaV. Gupta, Banaras Hindu University Department of Pediatrics, Institute of Medical Sciences Varanasi IndiaJ. Shukla, Banaras Hindu University Department of Pathology, Institute of Medical Sciences Varanasi India
Journal Indian Journal of PediatricsOnline ISSN 0973-7693Print ISSN 0019-5456
Journal Volume Volume 75
Journal Issue Volume 75, Number 7 / July, 2008 (Source: Indian Journal of Pediatrics)...
POSTED 08/21/2008 at 06:48 AM --
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Antitumor activity of bortezomib alone and in combination with trail in human acute myeloid leukemia
Acta Haematol 2008;120:19-30 (DOI:10.1159/000151511) (Source: Acta Haematologica)...
POSTED 08/21/2008 at 04:11 AM --
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Molecular detection of aml1-mtg8-positive cells in peripheral blood from a patient with isolated extramedullary relapse of t(8;21) acute myeloid leukemia
Molecular detection of AML1-MTG8-positive cells in peripheral blood from a patient with isolated extramedullary relapse of t(8;21) acute myeloid leukemia
Leukemia advance online publication, August 21, 2008. doi:10.1038/leu.2008.220
Authors: H Tamaki, S Yoshihara, T Fujioka, M Kawakami, Y Oka
& H Ogawa (Source: Leukemia)...
POSTED 08/20/2008 at 11:00 PM --
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Combination of 5-azacytidine and thalidomide for the treatment of myelodysplastic syndromes and acute myeloid leukemia
The treatment of myelodysplastic syndromes (MDS) remains a challenge to the clinician despite recent advances. Many patients will either not respond or will have only limited and/or brief responses to single-agent therapy. Eventually, 30% of patients with MDS will progress and develop acute myeloid leukemia (AML). New strategies are needed for these patients.5-Azacytidine (AZA) and thalidomide were administered to 40 patients with MDS or AML. AZA was given at a dose of 75 mg/m2 subcutaneously for 5 of 28 days together with thalidomide starting at a dose of 50 mg per day and increasing to 100 mg per. Six patients had refractory anemia (RA), 2 patients had RA with ringed sideroblasts, 10 patients had RA with excess blasts (RAEB), 1 patient had RAEB in transformation, 4 patients had chronic myelomonocytic leukemia, 1 patient had chronic idiopathic myelofibrosis, and 16 patients had AML. Thirty-six patients were evaluable for outcome.A hematologic improvement (HI) was observed in 15 of 36 patients (42%), stable disease was observed in 5 of 36 patients (14%), and 10 of 36 patients (28%) had disease progression. Six patients experienced complete remission (CR), 2 patients experienced an erythroid HI (HI-E), 1 patient experience an absolute neutrophil count HI (HI-ANC), 5 patients experienced a platelet HI (HI-P), and 7 patients had bilineage HI (HI-P and HI-ANC or an HI-E and HI-ANC). It was noteworthy that 9 of 14 patients with AML had a history of prior MDS, 2 of 9 patients achieved a CR, 4 of 9 patients had HI (HI-E and bilineage HI), and 1 patient had stable disease and was continuing treatment. DNA microarray analysis of 8 responders and 4 nonresponders revealed that the genes associated with cellular proliferation had higher expression levels in nonresponders.The current findings indicated that a combination of low-dose AZA and thalidomide was well tolerated and was effective therapy for the treatment of patients with MDS and AML arising from prior MDS. Cancer 2008. © 2008 American Cancer Society. (Source: Cancer)...
POSTED 08/19/2008 at 11:00 PM --
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Myeloid sarcoma presenting as a recurrent, multifocal nerve root entrapment syndrome
Abstract
Background Myeloid sarcoma is an extramedullary manifestation of haematologic malignancy, most commonly acute myeloid leukemia (AML),
which can cause neurological symptoms. Case description A 45-year-old male with a history of AML presented with a lumbosacral nerve root entrapment syndrome followed by cauda equina
compression, but without systemic signs of AML recurrence. MRI showed a mass compressing the spinal cord at level L5–S2. After
surgically removing the tumour pathologic examination yielded a myeloid sarcoma. Combined chemotherapy and radiation therapy
followed. Five months later the patient developed a thoracal (Th10–Th11) radiculopathy due to a relapse of the myeloid sarcoma,
followed by C8-Th1-radiculopathy caused by leptomeningeal spread. Conclusion This case forms the first description of recurrent, multifocal and progressive radiculopathy due to myeloid sarcoma. This
diagnosis should be considered in patients with radiculopathy with previous haematological malignancy and/or signs or symptoms
of such disease; the absence of systemic disease activity does not rule out myeloid sarcoma.
Content Type Journal ArticleCategory Clinical Study - Patient StudyDOI 10.1007/s11060-008-9679-1Authors
Wiebe C. Verra, University Medical Center Utrecht Department of Neurology, Rudolf Magnus Institute of Neuroscience (Internal Address C03.236) PO Box 85500 3508 GA Utrecht The NetherlandsTom J. Snijders, University Medical Center Utrecht Department of Neurology, Rudolf Magnus Institute of Neuroscience (Internal Address C03.236) PO Box 85500 3508 GA Utrecht The NetherlandsTatjana Seute, University Medical Center Utrecht Department of Neurology, Rudolf Magnus Institute of Neuroscience (Internal Address C03.236) PO Box 85500 3508 GA Utrecht The NetherlandsK. Sen Han, University Medical Center Utrecht Department of Neurosurgery Utrecht The NetherlandsH. Karel Nieuwenhuis, University Medical Center Utrecht Department of Haematology Utrecht The NetherlandsGeert Jan Rutten, St. Elisabeth Hospital Tilburg Department of Neurosurgery Postbus 90151 5000 LC Tilburg The Netherlands
Journal Journal of Neuro-OncologyOnline ISSN 1573-7373Print ISSN 0167-594X (Source: Journal of Neuro-Oncology)...
POSTED 08/19/2008 at 12:23 PM --
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Incidence of bacterial and fungal infections in newly diagnosed acute myeloid leukaemia patients younger than 65 yr treated with induction regimens including fludarabine: retrospective analysis of 224 cases
Objectives: Infections are the major cause of morbidity and mortality in patients with acute myeloid leukaemia (AML). They primarily occur during the first course of induction chemotherapy and may increase the risk of leukaemia relapse, due to a significant delay in consolidation therapy. The intensification of induction chemotherapy and the use of non-conventional drugs such as fludarabine are considered responsible for the increased risk of infections.Methods: In this study, we retrospectively analysed the infections occurred in 224 newly diagnosed AML patients [le]65 yr, consecutively treated between 1997 and 2002 with an induction regimen including fludarabine, arabinosyl cytosine and idarubicin, with or without etoposide (FLAI/FLAIE), in the context of three multicentric prospective trials (AML97, AML99, AML02).Results: During the induction phase, 146 (65%) patients experienced fever of undetermined origin (FUO), 30 (13%) and 47 (21%) patients had Gram-negative and positive bacteremias, respectively, and 10 (4%) patients developed a probable/proven invasive fungal infection (IFI). The fatality rate for Gram-negative, Gram-positive bacteremias and probable/proven IFI was 10%, 8% and 60% respectively. During consolidation, 75 (35%) patients had FUO, 43 (20%) and 40 (19%) patients had Gram-negative and positive bacteremias, respectively, and 5 (2%) patients developed a probable/proven IFI. The fatality rate for Gram-negative, Gram-positive bacteremias and probable/proven IFI was 14%, 5% and 80% respectively. Interestingly, the overall incidence of microbiologically documented infections during induction was 38% and the incidence of probable/proven IFIs during the induction/consolidation programme was 7%. No infections caused by viruses or opportunistic pathogens were observed neither during induction, nor during consolidation.Conclusions: These data, although retrospectively collected, suggest that fludarabine-based chemotherapy is not associated with an increased incidence of infections, in particular IFIs, compared to conventional regimens commonly used for AML induction. (Source: European Journal of Haematology)...
POSTED 08/18/2008 at 11:00 PM --
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Mitoxantrone: acute myeloid leukaemia: case report
(Source: Reactions)...
POSTED 08/18/2008 at 05:15 AM --
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Sequential continuous infusion of fludarabine and cytarabine associated with liposomal daunorubicin (daunoxome®) (flad) in primary refractory or relapsed adult acute myeloid leukemia patients
Abstract A large proportion of adult patients with acute myeloid leukemia (AML) relapse after treatment, and some of them are resistant
to primary induction chemotherapy. Sixty-one patients from seven hematological centers with poor-risk AML, primary refractory
(n = 16), or relapsed (n = 45) were treated with a salvage regimen, including fludarabine (2 days) and cytarabine (3 days) in a sequential continuous
infusion, associated with liposomal daunorubicin (3 days) (FLAD). Complete response rate was 44% and 56% for refractory and
relapsed patients, respectively, with an overall response rate of 52% (32 of 61). Twenty-two patients (36%) were resistant
to the salvage therapy. Seven patients (12%) died early during chemotherapy, four of them because of sepsis. Nineteen patients
in complete remission (CR) underwent a stem-cell transplant (SCT) procedure: five autologous, nine from a HL-A identical sibling,
and five from HL-A matched unrelated donors. Post-treatment aplasia and mucositis were major toxicities. Twenty patients (62.5%)
relapsed after this treatment in a median of 7.3 months; ten patients relapsed after a SCT procedure. Nine patients are alive
and disease free; three of them were rescued after a further cytotoxic treatment. The FLAD regimen proved to be an effective
and well-tolerated treatment, with acceptable toxicity in this group of high-risk patients. A better response rate was obtained
in the subgroup of relapsed patients, compared to patients treated for refractory disease. More then half (five of nine) of
long-surviving patients are those who were submitted to a transplant procedure; thus, the main indication for FLAD seems to
be to try to induce a rapid CR with minimum toxicity in order to perform a transplant as soon as possible.
Content Type Journal ArticleCategory Original ArticleDOI 10.1007/s00277-008-0571-zAuthors
Andrea Camera, Università Federico II Hematology Via Pansini, 5 80131 Naples ItalyCiro R. Rinaldi, Università Federico II Hematology Via Pansini, 5 80131 Naples ItalySalvatore Palmieri, A.O.R.N. Cardarelli Naples ItalyNicola Cantore, Ospedale Civile Avellino ItalyGiuseppina Mele, A.O.R.N. Cardarelli Naples ItalyVincenzo Mettivier, A.O.R.N. Cardarelli Naples ItalyEustachio Miraglia, Ospedale S.Giovanni Bosco Naples ItalyLucia Mastrullo, Ospedale San Gennaro Naples ItalyFrancesco Grimaldi, Università Federico II Hematology Via Pansini, 5 80131 Naples ItalyLuigia Luciano, Università Federico II Hematology Via Pansini, 5 80131 Naples ItalyAnna Guerriero, Università Federico II Hematology Via Pansini, 5 80131 Naples ItalyBruno Rotoli, Università Federico II Hematology Via Pansini, 5 80131 Naples ItalyFelicetto Ferrara, A.O.R.N. Cardarelli Naples Italy
Journal Annals of HematologyOnline ISSN 1432-0584Print ISSN 0939-5555 (Source: Annals of Hematology)...
POSTED 08/17/2008 at 11:12 AM --
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Mitoxantrone: acute myeloid leukaemia: case report.
Page: 27 (Source: Reactions Weekly)...
POSTED 08/17/2008 at 05:26 AM --
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Recurrent episodes of fever and pancytopenia due to haemophagocytosis during maintenance therapy for acute myeloid leukaemia
(Source: British Journal of Haematology)...
POSTED 08/14/2008 at 11:00 PM --
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Status of minimal residual disease testing in childhood haematological malignancies
In children with acute leukaemia, measurements of minimal residual disease (MRD) provide unique information on treatment response and have become a crucial component of contemporary treatment protocols. In acute lymphoblastic leukaemia (ALL), the most useful MRD assays are based on polymerase chain reaction (PCR) amplification of antigen-receptor genes, and on flow cytometric detection of abnormal immunophenotypes. The latter is the only MRD assay available for most patients with acute myeloid leukaemia (AML). PCR amplification of chromosomal breakpoints and fusion transcripts can also be used to track MRD in a minority of patients with ALL or AML. Because of the strong correlation between MRD levels and risk of relapse, several ongoing regimens include treatment intensification for children with higher MRD. Treatment de-intensification for patients with early MRD clearance is also being tested. In addition to their direct clinical application, MRD measurements can be used to better understand the molecular and cellular mechanisms of drug resistance in vivo. The identification of new markers of leukaemia and the use of increasingly sophisticated technologies for detection of rare cells should further facilitate routine monitoring of MRD and elucidate the features of drug-resistant leukaemic cells. (Source: British Journal of Haematology)...
POSTED 08/14/2008 at 11:00 PM --
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Advanced glycation end product (age)-induced proliferation of hel cells via receptor for age-related signal pathways.
Advanced glycation end product (AGE)-induced proliferation of HEL cells via receptor for AGE-related signal pathways.
Int J Oncol. 2008 Sep;33(3):493-501
Authors: Kim JY, Park HK, Yoon JS, Kim SJ, Kim ES, Ahn KS, Kim DS, Yoon SS, Kim BK, Lee YY
This study investigated whether advanced glycation end products (AGE) and RAGE (receptor for AGE) are involved in the proliferation of leukemia cells. AGE strongly induced the proliferation of primary acute myeloid leukemia (AML) cells and cell lines. MAP kinase, PI3K and JAK/STAT pathways were involved in cellular proliferation of HEL cells by AGE. RAGE antisense S-ODN effectively inhibited cell growth, induced apoptosis and reversed AGE-induced expression of targeting molecules in HEL cells. The study demonstrated for the first time that AGE directly induced human AML cell proliferation via the MAPK, PI3K and JAK/STAT pathways.
PMID: 18695878 [PubMed - in process] (Source: International Journal of Oncology)...
POSTED 08/13/2008 at 08:18 AM --
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Trisomy 22 as the sole abnormality is an important marker for the diagnosis of acute myeloid leukemia with inversion 16
Onkologie 2008;31:3 (DOI:10.1159/000141917) (Source: Karger Publishers)...
POSTED 08/13/2008 at 05:19 AM --
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Potential therapeutic applications of mirna-based technology in hematological malignancies.
Potential therapeutic applications of miRNA-based technology in hematological malignancies.
Curr Pharm Des. 2008;14(21):2040-50
Authors: Barbarotto E, Calin GA
MicroRNAs (miRNAs) are an abundant class of approximately 22-nucleotide-noncoding RNAs, which play important regulatory roles in animal and plant development: they are involved in gene expression at the posttranscriptional level by degrading or blocking translation of messenger RNA (mRNA) targets. miRNAs can induce RNA cleavage and chromatin modifications, and are implicated in apoptotic pathways and regulation of cell growth and proliferation. It is becoming clear that miRNAs play important roles in the regulation of gene expression during development, and our knowledge of the expression levels or function of miRNAs in normal and neoplastic cells is increasing. Accumulating experimental evidence suggests that different miRNAs are deregulated in primary human tumors and that many human miRNAs are located at genomic regions linked to cancer. miRNAs may be important regulators of mammalian hematopoiesis. They are involved in a variety of hematological malignancies, including acute lymphoblastic leukemia, acute myeloid leukemia, chronic myelogenous leukemia, chronic lymphocytic leukemia, diffuse large B-cell lymphoma, and primary effusion lymphoma. Here, we provide background on the biogenesis and function of miRNAs and discuss potential therapeutic applications of miRNA-based technology in hematological malignancies.
PMID: 18691114 [PubMed - in process] (Source: Current Pharmaceutical Design)...
POSTED 08/12/2008 at 08:49 AM --
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A limited number of 5-azacitidine cycles can be effective treatment in mds
Abstract Hypomethylating agents, such as 5-azacitidine (5-AZA) and 5-aza-2’-deoxycytidine (decitabine), have recently been approved
for the treatment of myelodysplastic syndromes (MDS). Several randomized trials have shown favorable results concerning response
rate, survival, transformation to acute leukemia, and quality of life. In these trials, treatment was administered continuously
until progression. In the retrospective study presented here, we evaluated the outcome of patients with higher risk MDS or
secondary acute myeloid leukemia (sAML) treated with a limited number of 5-AZA cycles. A total of 32 patients received 5-AZA
alone (n = 30) or in combination with valproic acid and all-trans retinoic acid (n = 2). 5-AZA was administered subcutaneously at a fixed dose of 75 mg/m2 daily for 7 days and repeated every 28 days. 5-AZA was given for a median of four courses. Treatment was continued for two
more cycles as consolidation in patients who had achieved complete remission (CR), marrow CR, or stable disease with hematologic
improvement. The overall response rate was 50% according to the modified International Working Group criteria. Complete remissions
were achieved in 15.6% and stable disease in 34.4% of patients. Peripheral blood counts normalized in 6.3% of patients while
hematologic improvement was achieved in 25%. The median time to AML in responding patients was 45 weeks, while AML occurred
after a median of 14 weeks in non-responding patients (P = .038). The median survival of all patients was 60 weeks; the median survival of responders was 74 weeks compared with 26 weeks
in non-responders (P = .047). In this retrospective analysis, 5-AZA was associated with a survival advantage in responding patients with higher
risk MDS or sAML. These favorable results suggest that patients may benefit even from a limited number of courses of 5-AZA.
A randomized controlled clinical trial is required to prospectively validate these findings.
Content Type Journal ArticleCategory Original ArticleDOI 10.1007/s00277-008-0583-8Authors
Catharina Müller-Thomas, Technical University of Munich III Department of Medicine Ismaningerstr. 15 81675 Munich GermanyTibor Schuster, Technical University of Munich Institute for Statistics Munich GermanyChristian Peschel, Technical University of Munich III Department of Medicine Ismaningerstr. 15 81675 Munich GermanyKatharina S. Götze, Technical University of Munich III Department of Medicine Ismaningerstr. 15 81675 Munich Germany
Journal Annals of HematologyOnline ISSN 1432-0584Print ISSN 0939-5555 (Source: Annals of Hematology)...
POSTED 08/12/2008 at 02:27 AM --
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Pituitary apoplexy during induction chemotherapy for acute myeloid leukaemia
(Source: British Journal of Haematology)...
POSTED 08/10/2008 at 11:00 PM --
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Ifn-gamma-producing human invariant nkt cells promote tumor-associated antigen-specific cytotoxic t cell responses.
IFN-gamma-producing human invariant NKT cells promote tumor-associated antigen-specific cytotoxic T cell responses.
J Immunol. 2008 Aug 15;181(4):2446-54
Authors: Moreno M, Molling JW, von Mensdorff-Pouilly S, Verheijen RH, Hooijberg E, Kramer D, Reurs AW, van den Eertwegh AJ, von Blomberg BM, Scheper RJ, Bontkes HJ
CD1d-restricted invariant NKT (iNKT) cells can enhance immunity to cancer or prevent autoimmunity, depending on the cytokine profile secreted. Antitumor effects of the iNKT cell ligand alpha-galactosylceramide (alphaGC) and iNKT cell adoptive transfer have been demonstrated in various tumor models. Together with reduced numbers of iNKT cells in cancer patients, which have been linked to poor clinical outcome, these data suggest that cancer patients may benefit from therapy aiming at iNKT cell proliferation and activation. Herein we present results of investigations on the effects of human iNKT cells on Ag-specific CTL responses. iNKT cells were expanded using alphaGC-pulsed allogeneic DC derived from the acute myeloid leukemia cell line MUTZ-3, transduced with CD1d to enhance iNKT cell stimulation, and with IL-12 to stimulate type 1 cytokine production. Enhanced activation and increased IFN-gamma production was observed in iNKT cells, irrespective of CD4 expression, upon stimulation with IL-12-overexpressing dendritic cells. IL-12-stimulated iNKT cells strongly enhanced the MART-1 (melanoma Ag recognized by T cell 1)-specific CD8(+) CTL response, which was dependent on iNKT cell-derived IFN-gamma. Furthermore, autologous IL-12-overexpressing dendritic cells, loaded with Ag as well as alphaGC, was superior in stimulating both iNKT cells and Ag-specific CTL. This study shows that IL-12-overexpressing allogeneic dendritic cells expand IFN-gamma-producing iNKT cells, which may be more effective against tumors in vivo. Furthermore, the efficacy of autologous Ag-loaded DC vaccines may well be enhanced by IL-12 overexpression and loading with alphaGC.
PMID: 18684935 [PubMed - in process] (Source: Journal of Immunology)...
POSTED 08/10/2008 at 03:52 AM --
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Ifn-{gamma}-producing human invariant nkt cells promote tumor-associated antigen-specific cytotoxic t cell responses.
IFN-{gamma}-Producing Human Invariant NKT Cells Promote Tumor-Associated Antigen-Specific Cytotoxic T Cell Responses.
J Immunol. 2008 Aug 15;181(4):2446-54
Authors: Moreno M, Molling JW, von Mensdorff-Pouilly S, Verheijen RH, Hooijberg E, Kramer D, Reurs AW, van den Eertwegh AJ, von Blomberg BM, Scheper RJ, Bontkes HJ
CD1d-restricted invariant NKT (iNKT) cells can enhance immunity to cancer or prevent autoimmunity, depending on the cytokine profile secreted. Antitumor effects of the iNKT cell ligand alpha-galactosylceramide (alphaGC) and iNKT cell adoptive transfer have been demonstrated in various tumor models. Together with reduced numbers of iNKT cells in cancer patients, which have been linked to poor clinical outcome, these data suggest that cancer patients may benefit from therapy aiming at iNKT cell proliferation and activation. Herein we present results of investigations on the effects of human iNKT cells on Ag-specific CTL responses. iNKT cells were expanded using alphaGC-pulsed allogeneic DC derived from the acute myeloid leukemia cell line MUTZ-3, transduced with CD1d to enhance iNKT cell stimulation, and with IL-12 to stimulate type 1 cytokine production. Enhanced activation and increased IFN-gamma production was observed in iNKT cells, irrespective of CD4 expression, upon stimulation with IL-12-overexpressing dendritic cells. IL-12-stimulated iNKT cells strongly enhanced the MART-1 (melanoma Ag recognized by T cell 1)-specific CD8(+) CTL response, which was dependent on iNKT cell-derived IFN-gamma. Furthermore, autologous IL-12-overexpressing dendritic cells, loaded with Ag as well as alphaGC, was superior in stimulating both iNKT cells and Ag-specific CTL. This study shows that IL-12-overexpressing allogeneic dendritic cells expand IFN-gamma-producing iNKT cells, which may be more effective against tumors in vivo. Furthermore, the efficacy of autologous Ag-loaded DC vaccines may well be enhanced by IL-12 overexpression and loading with alphaGC.
PMID: 18684935 [PubMed - in process] (Source: Journal of Immunology)...
POSTED 08/09/2008 at 04:08 AM --
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Human acute leukemia cells injected in nod/ltsz-scid/il-2r[gamma] null mice generate a faster and more efficient disease compared to other nod/scid-related strains
Transplantation of human acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL) primary cells and cell lines in different strains of immunodeficient mice has led to preclinical models extensively used to investigate acute leukemia stem cells, biology and drug sensitivity. We studied the engraftment kinetics of AML and ALL cell lines and primary cells in 3 strains of NOD.CB17-Prkdcscid (NOD/scid, NS)-related mice (NOD.Cg-PrkdcscidB2mtm1Unc/J, abbreviated NOD/scid/[beta]2 null, NSB; and NOD.Cg-PrkdcscidIl2rgtm1Wjll/SzJ, abbreviated NOD/scid/IL-2R[gamma] null, NSG). The engraftment of human malignant cells was investigated by means of clinicopathological criteria, flow cytometry, PCR and immunohistochemistry. In NSG mice, we observed a significantly faster development of leukemia-related symptoms and a higher percentage of leukemia cells in the blood, in the marrow and in the spleen. The leukemia-related angiogenic switch (measured as the number of circulating endothelial cells and progenitors) was faster in NSG compared to NS and NSB mice. These models will be instrumental to studies on leukemia-initiating stem cells, leukemia biology, preclinical treatment studies, and to obtain patient-specific preclinical models to design and investigate patient-tailored therapies. © 2008 Wiley-Liss, Inc. (Source: International Journal of Cancer)...
POSTED 08/08/2008 at 11:00 PM --
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