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Article: The biology and treatment of myelodysplastic syndromes.

Raza, Azra / Galili, Naomi

Rinsho ketsueki] The Japanese journal of clinical hematology

2013 Volume 54, Issue 10, Page(s) 1730–1736

MeSH term(s)	Animals ; Genetic Predisposition to Disease ; Humans ; MicroRNAs/genetics ; Mutation/genetics ; Myelodysplastic Syndromes/genetics ; Myelodysplastic Syndromes/metabolism ; Myelodysplastic Syndromes/therapy ; Ribosomes/genetics ; Ribosomes/metabolism ; Stem Cells/cytology
Chemical Substances	MicroRNAs
Language	English
Publishing date	2013-10
Publishing country	Japan
Document type	Journal Article ; Review
ZDB-ID	390900-1
ISSN	0485-1439
ISSN	0485-1439
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Article ; Online: The genetic basis of phenotypic heterogeneity in myelodysplastic syndromes.

Raza, Azra / Galili, Naomi

Nature reviews. Cancer

2012 Volume 12, Issue 12, Page(s) 849–859

Abstract: Myelodysplastic syndromes (MDS) are malignant clonal disorders of haematopoietic stem cells and their microenvironment, affecting older individuals (median age ∼70 years). Unique features that are associated with MDS - but which are not necessarily ... ...

Abstract	Myelodysplastic syndromes (MDS) are malignant clonal disorders of haematopoietic stem cells and their microenvironment, affecting older individuals (median age ∼70 years). Unique features that are associated with MDS - but which are not necessarily present in every patient with MDS - include excessive apoptosis in maturing clonal cells, a pro-inflammatory bone marrow microenvironment, specific chromosomal abnormalities, abnormal ribosomal protein biogenesis, the presence of uniparental disomy, and mutations affecting genes involved in proliferation, methylation and epigenetic modifications. Although emerging insights establish an association between molecular abnormalities and the phenotypic heterogeneity of MDS, their origin and progression remain enigmatic.
MeSH term(s)	Apoptosis/genetics ; Chromatin/genetics ; Chromosome Aberrations ; Epigenesis, Genetic ; Gene Expression Profiling ; Genes, Tumor Suppressor ; Humans ; MicroRNAs ; Mutation ; Myelodysplastic Syndromes/genetics ; Myelodysplastic Syndromes/pathology ; Oncogenes ; Ribosomes/genetics ; Ribosomes/metabolism ; Spliceosomes/genetics ; Uniparental Disomy/genetics ; Uniparental Disomy/pathology
Chemical Substances	Chromatin ; MicroRNAs
Language	English
Publishing date	2012-11-21
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	2062767-1
ISSN	1474-1768 ; 1474-175X
ISSN (online)	1474-1768
ISSN	1474-175X
DOI	10.1038/nrc3321
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Zs.A 5563: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
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Article ; Online: Pharmacotherapy of myelodysplastic syndromes.

Galili, Naomi / Raza, Azra

Expert opinion on pharmacotherapy

2010 Volume 11, Issue 11, Page(s) 1889–1899

Abstract: Importance of the field: Despite the remarkable progress in the treatment of patients with myelodysplastic syndromes (MDS) in the past decade, response to the hypomethylating agents azacitidine and decitabine in non-del(5q) MDS patients remains at ... ...

Abstract	Importance of the field: Despite the remarkable progress in the treatment of patients with myelodysplastic syndromes (MDS) in the past decade, response to the hypomethylating agents azacitidine and decitabine in non-del(5q) MDS patients remains at approximately 50%, leaving half of patients needing treatment with essentially no options. As biologic insight into the molecular pathways that account for disease evolution and clinical heterogeneity is expanded, the arsenal of potential drugs that may elicit significant response is also increasing. One of the greatest challenges for the treating physician is to decide when to initiate therapy and which therapy (approved drug or newer agents still in clinical trial) is likely to be the most beneficial. While there is no single answer to these issues, there are several approaches that may be considered, and these are addressed in this review. Areas covered in this review: This review examines the clinical outcomes of the FDA-approved drugs as well as of the promising new therapies that are in current clinical trials. What the reader will gain: The clinician now has multiple treatment options for patients with MDS. It is important to consider multiple factors before initiating therapy with disease-modifying drugs. This review presents some of the decision-making approaches that are in practice at present. Take home message: For the first time, various treatment options are available for patients with MDS. In light of the intense efforts now in progress, the next decade promises to be one of hope and excitement for both MDS patients and treating clinicians.
MeSH term(s)	Azacitidine/analogs & derivatives ; Azacitidine/therapeutic use ; DNA Methylation ; Drug Approval/legislation & jurisprudence ; Erythropoietin/therapeutic use ; Humans ; Iron Chelating Agents/therapeutic use ; Myelodysplastic Syndromes/drug therapy ; Recombinant Proteins ; Thalidomide/analogs & derivatives ; Thalidomide/therapeutic use ; United States ; United States Food and Drug Administration
Chemical Substances	Iron Chelating Agents ; Recombinant Proteins ; Erythropoietin (11096-26-7) ; Thalidomide (4Z8R6ORS6L) ; decitabine (776B62CQ27) ; lenalidomide (F0P408N6V4) ; Azacitidine (M801H13NRU)
Language	English
Publishing date	2010-08
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	2001535-5
ISSN	1744-7666 ; 1465-6566
ISSN (online)	1744-7666
ISSN	1465-6566
DOI	10.1517/14656566.2010.485613
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Article ; Online: Prognosis in myelodysplastic syndromes: are the new classifications useful?

Galili, Naomi / Raza, Azra

Current hematologic malignancy reports

2010 Volume 3, Issue 1, Page(s) 19–22

Abstract: Increased understanding of the biologic and clinical parameters that define subgroups of myelodysplastic syndromes has led to continuing refinement of classification strategies for diagnostic and prognostic use. The French-American-British classification, ...

Abstract	Increased understanding of the biologic and clinical parameters that define subgroups of myelodysplastic syndromes has led to continuing refinement of classification strategies for diagnostic and prognostic use. The French-American-British classification, based primarily on morphology, was modified by the World Health Organization system to include the negative impact of multilineage dysplasias and higher blast counts. In addition, this system identifies a distinct clinical subgroup characterized by an isolated chromosome 5 deletion. The International Prognostic Scoring System was created to calculate prognosis, risk of transformation to acute myeloid leukemia, and median survival times. However, therapeutic decisions cannot be solely guided by these systems, and the clinician must decide whether the intent is curative or palliative. Clinical symptoms and degree of transfusion dependency will dictate the degree of therapeutic intervention.
MeSH term(s)	Humans ; Myelodysplastic Syndromes/classification ; Myelodysplastic Syndromes/diagnosis ; Prognosis ; World Health Organization
Language	English
Publishing date	2010-04-28
Publishing country	United States
Document type	Journal Article
ZDB-ID	2229765-0
ISSN	1558-822X ; 1558-8211
ISSN (online)	1558-822X
ISSN	1558-8211
DOI	10.1007/s11899-008-0004-z
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Article ; Online: Clinical implications of gene expression profiling in myelodysplastic syndromes: recognition of ribosomal and translational gene dysregulation and development of predictive assays.

Galili, Naomi / Raza, Azra

Best practice & research. Clinical haematology

2009 Volume 22, Issue 2, Page(s) 223–237

Abstract: Myelodysplastic syndromes (MDS) are a group of haematopoietic stem cell disorders that pose a unique challenge for gene expression profiling by virtue of their inherent heterogeneity. Despite monoclonality of MDS, the marrow picture is complicated by the ...

Abstract	Myelodysplastic syndromes (MDS) are a group of haematopoietic stem cell disorders that pose a unique challenge for gene expression profiling by virtue of their inherent heterogeneity. Despite monoclonality of MDS, the marrow picture is complicated by the presence of not only stromal cells but also by varying stages of differentiating diseased cells belonging to all three lineages. Now that reproducible results can be obtained from nanograms of RNA, it is possible to derive useful information from even a limited number of cells; for example, dysregulation of ribosomal and translational genes was detected in MDS patients compared to controls using a small number of CD34+ cells. Gene expression profiling in MDS patients treated with lenalidomide or 5-azacitidine+thalidomide yielded signatures which differentiated responders from non-responders. These biologic and clinical insights are providing the framework on which to build a new model of these diseases which, despite their heterogeneity, manifest certain unifying themes.
MeSH term(s)	Antigens, CD34/genetics ; Azacitidine/analogs & derivatives ; Azacitidine/therapeutic use ; Cell Proliferation ; Drug Resistance, Neoplasm/genetics ; Gene Expression Profiling/methods ; Gene Expression Regulation, Neoplastic/physiology ; Humans ; Myelodysplastic Syndromes/drug therapy ; Myelodysplastic Syndromes/genetics ; Protein Biosynthesis/genetics ; Ribosomes/genetics ; Thalidomide/analogs & derivatives ; Thalidomide/therapeutic use
Chemical Substances	Antigens, CD34 ; Thalidomide (4Z8R6ORS6L) ; decitabine (776B62CQ27) ; lenalidomide (F0P408N6V4) ; Azacitidine (M801H13NRU)
Language	English
Publishing date	2009-06
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	2048027-1
ISSN	1532-1924 ; 1521-6926
ISSN (online)	1532-1924
ISSN	1521-6926
DOI	10.1016/j.beha.2009.04.006
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Article ; Online: MDS: Refining existing therapy through improved biologic insights.

Schecter, Jordan / Galili, Naomi / Raza, Azra

Blood reviews

2012 Volume 26, Issue 2, Page(s) 73–80

Abstract: Advances in therapy can essentially be measured using two parameters; introduction of a new agent which benefits an increased number of patients over prevailing treatments or more selective use of an existing drug by matching it to the biologic ... ...

Abstract	Advances in therapy can essentially be measured using two parameters; introduction of a new agent which benefits an increased number of patients over prevailing treatments or more selective use of an existing drug by matching it to the biologic characteristics associated with response. In reviewing the therapeutic landscape of myelodysplastic syndromes (MDS), both should be applied to gauge the advances in therapy. While several new drugs are currently in clinical trials for the treatment of MDS, three drugs were approved for use in the last decade and sufficient time has elapsed to take stock of the benefit they have produced in the outcome of patients both in terms of survival and quality of life. For the two hypomethylating agents, response remains limited to 50% patients at best, and no strategy has evolved to allow for pre-selection of likely responders, however, 5-azacytidine has been associated with improvement in the survival of higher risk patients. The benefit of lenalidomide was found to be greater for del(5q) patients with transfusion dependent anemia and lower risk disease right from the start, although a quarter of the non-del(5q) patients also experienced complete transfusion independence with this agent. It is in this latter group of non-del(5q) cases that a strategy for potentially preselecting likely responders is suggested by the finding of an expression profile associated with response. In this paper, we will focus on defining our current understanding of the mechanisms of action of the existing FDA approved drugs in order to identify therapeutic strategies that are suitable for specific MDS subtypes. We expect that through advancing biologic insights, the use of such therapies will become more selective and refined.
MeSH term(s)	Antineoplastic Agents/therapeutic use ; Drug Approval/legislation & jurisprudence ; Humans ; Myelodysplastic Syndromes/drug therapy ; Quality of Life ; Survival Rate ; United States ; United States Food and Drug Administration
Chemical Substances	Antineoplastic Agents
Language	English
Publishing date	2012-03
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	639015-8
ISSN	1532-1681 ; 0268-960X
ISSN (online)	1532-1681
ISSN	0268-960X
DOI	10.1016/j.blre.2011.11.001
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Zs.A 2207: Show issues

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Article ; Online: Immunomodulatory drugs in myelodysplastic syndromes.

Galili, Naomi / Raza, Azra

Expert opinion on investigational drugs

2006 Volume 15, Issue 7, Page(s) 805–813

Abstract: This review summarises the mechanism of action of immunomodulatory analogues of thalidomide and their use in myelodysplastic syndromes. Thalidomide was found to have a response rate of approximately 20% in these patients. Lenalidomide--which is more ... ...

Abstract	This review summarises the mechanism of action of immunomodulatory analogues of thalidomide and their use in myelodysplastic syndromes. Thalidomide was found to have a response rate of approximately 20% in these patients. Lenalidomide--which is more potent and less toxic than thalidomide--has been used in three clinical trials and produced the best responses (60 - > 90%) in low- and intermediate-1-risk transfusion-dependent patients with del(5q). The responses are purely erythroid in nature, and are associated with major cytogenetic responses in > 50% of the del(5q) patients. Non-del(5q) low- and intermediate-1-risk transfusion-dependent patients also had a approximately 25% incidence of transfusion independence following therapy with lenalidomide. Median time to response is approximately 4 weeks and 90% of patients respond within 12 weeks. The precise mechanism of action remains unknown but anticytokine, antiangiogenic and immunomodulatory properties are thought to play a role.
MeSH term(s)	Adult ; Aged ; Aged, 80 and over ; Angiogenesis Inhibitors/adverse effects ; Angiogenesis Inhibitors/pharmacology ; Angiogenesis Inhibitors/therapeutic use ; Animals ; Apoptosis/drug effects ; Blood Transfusion ; Cell Lineage ; Cells, Cultured/drug effects ; Chromosome Deletion ; Chromosomes, Human, Pair 5/ultrastructure ; Clinical Trials as Topic ; Cytokines/physiology ; Drug Evaluation, Preclinical ; Drugs, Investigational/therapeutic use ; Erythrocyte Transfusion ; Erythropoiesis/drug effects ; Female ; Hematopoietic Stem Cells/drug effects ; Humans ; Immunologic Factors/adverse effects ; Immunologic Factors/pharmacology ; Immunologic Factors/therapeutic use ; Lenalidomide ; Male ; Middle Aged ; Myelodysplastic Syndromes/drug therapy ; Myelodysplastic Syndromes/genetics ; Myelodysplastic Syndromes/therapy ; NF-kappa B/antagonists & inhibitors ; Neutropenia/chemically induced ; Pilot Projects ; Thalidomide/adverse effects ; Thalidomide/analogs & derivatives ; Thalidomide/chemistry ; Thalidomide/pharmacology ; Thalidomide/therapeutic use ; Thrombocytopenia/chemically induced ; Tumor Necrosis Factor-alpha/antagonists & inhibitors ; Tumor Necrosis Factor-alpha/physiology
Chemical Substances	Angiogenesis Inhibitors ; Cytokines ; Drugs, Investigational ; Immunologic Factors ; NF-kappa B ; Tumor Necrosis Factor-alpha ; Thalidomide (4Z8R6ORS6L) ; pomalidomide (D2UX06XLB5) ; Lenalidomide (F0P408N6V4)
Language	English
Publishing date	2006-06-01
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	1182884-5
ISSN	1744-7658 ; 0967-8298 ; 1354-3784
ISSN (online)	1744-7658
ISSN	0967-8298 ; 1354-3784
DOI	10.1517/13543784.15.7.805
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Article ; Online: Isolation of specific and biologically active peptides that bind cells from patients with acute myeloid leukemia (AML)

Devemy Emmanuelle / Galili Naomi / Raza Azra

Journal of Hematology & Oncology, Vol 1, Iss 1, p

2008 Volume 8

Abstract: Abstract Purpose In a departure from conventional strategies to improve treatment outcome for myeloid malignancies, we report the isolation of leukemia-specific peptides using a phage display library screened with freshly obtained human myeloid leukemia ... ...

Abstract	Abstract Purpose In a departure from conventional strategies to improve treatment outcome for myeloid malignancies, we report the isolation of leukemia-specific peptides using a phage display library screened with freshly obtained human myeloid leukemia cells. Results A phage display library was screened by 5 rounds of biopanning with freshly isolated human AML cells. Individual colonies were randomly picked and after purification, biologic activity (growth and differentiation) on fresh AML cells was profiled. Ten peptides were synthesized for further biological studies. Multiple peptides were found to selectively bind to acute myeloid leukemia (AML) cells. The peptides bound to leukemia cells, were internalized and could induce proliferation and/or differentiation in the target patient cells. Two of the peptides, HP-A2 and HP-G7, appeared to have a novel mechanism of inducing differentiation since they did not cause G1 arrest in cycling cells even as the expression of the differentiation marker CD11b increased. Conclusion Peptide induced differentiation of leukemia cells offers a novel treatment strategy for myeloid malignancies, whereas their ability to induce proliferation could be harnessed to make cells more sensitive to chemotherapy. Conceptually, these leukemia specific peptides can also be used to refine diagnosis, document minimal residual disease, and selectively deliver toxins to malignant cells.
Keywords	Diseases of the blood and blood-forming organs ; RC633-647.5 ; Specialties of internal medicine ; RC581-951 ; Internal medicine ; RC31-1245 ; Medicine ; R ; DOAJ:Internal medicine ; DOAJ:Medicine (General) ; DOAJ:Health Sciences ; Neoplasms. Tumors. Oncology. Including cancer and carcinogens ; RC254-282 ; DOAJ:Oncology
Subject code	610
Language	English
Publishing date	2008-07-01T00:00:00Z
Publisher	BioMed Central
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article: Lenalidomide for myelodysplastic syndromes: finally, hope not hype.

Raza, Azra / Galili, Naomi

Nature clinical practice. Oncology

2005 Volume 2, Issue 8, Page(s) 390–391

Language	English
Publishing date	2005-08-24
Publishing country	England
Document type	Comment ; Journal Article
ZDB-ID	2173301-6
ISSN	1743-4254
ISSN	1743-4254
DOI	10.1038/ncponc0244
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Article ; Online: Defective ribosome biogenesis in myelodysplastic syndromes.

Galili, Naomi / Qasim, Samir Ahmed / Raza, Azra

Haematologica

2009 Volume 94, Issue 10, Page(s) 1336–1338

MeSH term(s)	Humans ; Myelodysplastic Syndromes/genetics ; Myelodysplastic Syndromes/pathology ; Ribosomes/genetics ; Ribosomes/pathology ; Stem Cells/pathology
Language	English
Publishing date	2009-09-30
Publishing country	Italy
Document type	Comment ; Editorial ; Research Support, Non-U.S. Gov't
ZDB-ID	2333-4
ISSN	1592-8721 ; 0017-6567 ; 0390-6078
ISSN (online)	1592-8721
ISSN	0017-6567 ; 0390-6078
DOI	10.3324/haematol.2009.012021
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