Search Our Scientific Publications & Authors

Blood 2020 Apr 29. Epub 2020 Apr 29.

University of Pavia, Pavia, Italy.

The 2016 revision of the World Health Organization (WHO) classification of tumors of hematopoietic and lymphoid tissues is characterized by a closer integration of morphology and molecular genetics. Notwithstanding, the myelodysplastic syndrome (MDS) with isolated del(5q) remains so far the only MDS subtype defined by a genetic abnormality. About half of MDS patients carry somatic mutations in spliceosome genes, with SF3B1 being the most commonly mutated one. Read More

BMJ Case Rep 2019 Apr 20;12(4). Epub 2019 Apr 20.

Department of Hematology and Medical Oncology, Oakland University William Beaumont School of Medicine, Royal Oak, Michigan, USA.

A patient with a diagnosis of myelodysplastic syndrome (MDS) with isolated 5q deletion underwent repeat bone marrow biopsy to assess haematological response after 6 months of initial lenalidomide therapy. Subsequent bone marrow biopsies revealed persistent MDS with del(5q) in addition to a small atypical mast cell population with >25% of mast cells with spindle-shaped morphology and immunohistochemistry characteristics consistent with mastocytosis. Molecular testing on the bone marrow was positive for D816V and the patient was diagnosed with systemic mastocytosis (SM) with an associated haematological neoplasm. Read More

Genes Chromosomes Cancer 2019 08 14;58(8):551-557. Epub 2019 Feb 14.

Department of Pathology, University of Utah, Salt Lake City, Utah.

The t(7;21)(p22;q22) resulting in RUNX1-USP42 fusion, is a rare but recurrent cytogenetic abnormality associated with acute myeloid leukemia (AML) and myelodysplastic syndromes. The prognostic significance of this translocation has not been well established due to the limited number of patients. Herein, we report three pediatric AML patients with t(7;21)(p22;q22). Read More

BMJ Open 2018 07 23;8(7):e019955. Epub 2018 Jul 23.

Department of Statistics and Biostatistics, Celgene Corporation, Summit, New Jersey, USA.

Objectives: Treatment patterns for patients with myelodysplastic syndromes (MDS) outside clinical trials are not well described. Our objective was to evaluate treatment patterns and patient characteristics that influence time to disease-modifying therapy in patients with MDS in the USA.

Design, Participants And Outcome Measures: Patients with MDS treated with erythropoiesis-stimulating agents (ESAs), iron chelation therapy, lenalidomide (LEN) and the hypomethylating agents (HMAs) azacitidine and decitabine, were retrospectively identified in the GE Centricity Electronic Medical Record database between January 2006 and February 2014; LEN and HMAs were defined as 'disease-modifying' therapies. Read More

Blood 2018 07;132(1):112

University of Toronto.

Eur J Haematol 2018 Jul 22;101(1):78-85. Epub 2018 May 22.

Department of Medicine, Institute of Hematology and Center for Hemato-Oncology Research (C.R.E.O.), University of Perugia, Perugia, Italy.

Objective: The most typical cytogenetic aberration in myelodysplastic syndromes is del(5q), which, when isolated, is associated with refractory anaemia and good prognosis. Based on high rates of erythroid response and transfusion independence, Lenalidomide (LEN) became the standard treatment. This multi-centre study was designed to supplement Italian Registry data on LEN by addressing prescription, administration appropriateness, haematological and cytogenetic responses and disease evolution. Read More

Methods Mol Biol 2017 ;1541:209-222

Victorian Cancer Cytogenetics Service, St. Vincent's Hospital, 41 Victoria Parade, Fitzroy, Melbourne, VIC, 3065, Australia.

Cytogenetic analysis has an essential role in diagnosis, classification, and prognosis of myelodysplastic syndromes (MDS). Some cytogenetic abnormalities are sufficiently characteristic of MDS to be considered MDS defining in the appropriate clinical context. MDS with isolated del(5q) is the only molecularly defined MDS subtype. Read More

Oncotarget 2016 10;7(42):68023-68032

MDS and MPN Centre, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, China.

Background: In vitro colony-forming unit cell (CFU-C) assays are usually-used to detect the quantitative and qualitative features of haematopoietic stem cells (HSCs). We studies CFU-C assays in bone marrow samples from 365 consecutive subjects with newly-diagnosed myelodysplastic syndrome (MDS). Data were interrogated for associations with prognosis. Read More

Sci Transl Med 2016 05;8(338):338ra67

University of Washington, Seattle, WA 98195, USA.

Diamond Blackfan anemia (DBA) and myelodysplastic syndrome (MDS) with isolated del(5q) are severe macrocytic anemias; although both are associated with impaired ribosome assembly, why the anemia occurs is not known. We cultured marrow cells from DBA (n = 3) and del(5q) MDS (n = 6) patients and determined how heme (a toxic chemical) and globin (a protein) are coordinated. We show that globin translation initiates slowly, whereas heme synthesis proceeds normally. Read More

Lancet Haematol 2015 May 6;2(5):e212-21. Epub 2015 May 6.

Department of Haematological Medicine, King's College London School of Medicine, Rayne Institute, King's College London, London, UK; Department of Haematology, King's College Hospital, King's College London, London, UK. Electronic address:

Background: A mechanism for clonal growth advantage in isolated del(5q) disease remains elusive. CSNK1A1 resides on the critically deleted region, and deletion of this gene has been shown in mouse knockout and transplantation studies to produce some characteristics of bone marrow failure, including a proliferative advantage. We aimed to establish the frequency, nature, and clinical association of CSNK1A1 mutations in patients with myelodysplastic syndrome and associated myeloid neoplasms. Read More

Ann Oncol 2016 Jan 26;27(1):62-8. Epub 2015 Oct 26.

Malignant Hematology Department, Moffitt Cancer Center, Tampa, USA.

The treatment of patients with myelodysplastic syndromes (MDS) begins with assessment of karyotype and risk. Lenalidomide is approved for the treatment of patients who have transfusion-dependent anemia due to lower-risk MDS with chromosome 5q deletion (del(5q)) with or without additional cytogenetic abnormalities, and isolated del(5q) only in the European Union. Mounting evidence suggests that lenalidomide is effective not only in reducing red blood cell (RBC) transfusion burden, but also in modifying the disease natural history by suppressing the malignant clone. Read More

Leuk Res 2015 Sep 21. Epub 2015 Sep 21.

Department of Hematology, Oncology and Stem Cell Transplantation, Medical Faculty, RWTH Aachen University, Aachen, Germany.

Myelodysplastic syndrome (MDS) associated with an acquired, isolated deletion of chromosome 5q (del (5q) MDS), represent a clonal disorder of hematopoiesis and a clinically distinct entity of MDS. Treatment of del (5q) MDS with the drug lenalidomide has significantly improved quality of life leading to transfusion independence and complete cytogenetic response rates (CCR) in the majority of patients. Telomeres are located at the end of eukaryotic chromosomes and are linked to replicative history/potential as well as genetic (in) stability of hematopoietic stem cells. Read More

Gen Physiol Biophys 2015 Oct;34(4):399-406

A specific type of myelodysplastic syndrome (MDS) is associated with isolated deletion on the long arm of chromosome 5, i.e., 5q-syndrome (del(5q)). Read More

Front Oncol 2014 23;4:264. Epub 2014 Sep 23.

Immunology Program and Malignant Hematology Program, H. Lee Moffitt Cancer Center and Research Institute , Tampa, FL , USA.

Myelodysplastic syndromes (MDS) represent a hematologically diverse group of myeloid neoplasms, however, one subtype characterized by an isolated deletion of chromosome 5q [del(5q)] is pathologically and clinically distinct. Patients with del(5q) MDS share biological features that account for the profound hypoplastic anemia and unique sensitivity to treatment with lenalidomide. Ineffective erythropoiesis in del(5q) MDS arises from allelic deletion of the ribosomal processing S-14 (RPS14) gene, which leads to MDM2 sequestration with consequent p53 activation and erythroid cell death. Read More

Eur J Haematol 2015 Jul 31;95(1):27-34. Epub 2014 Oct 31.

Institute of Hematology and Blood Transfusion, Prague, Czech Republic.

Downregulation of cereblon (CRBN) gene expression is associated with resistance to the immunomodulatory drug lenalidomide and poor survival outcomes in multiple myeloma (MM) patients. However, the importance of CRBN gene expression in patients with myelodysplastic syndrome (MDS) and its impact on lenalidomide therapy are not clear. In this study, we evaluate cereblon expression in mononuclear cells isolated from bone marrow [23 lower risk MDS patients with isolated 5q deletion (5q-), 37 lower risk MDS patients with chromosome 5 without the deletion of long arms (non-5q-), and 24 healthy controls] and from peripheral blood (38 patients with 5q-, 52 non-5q- patients and 25 healthy controls) to gain insight into, firstly, the role of cereblon in lower risk MDS patients with or without 5q deletion and, secondly, into the mechanisms of lenalidomide action. Read More

Clin Chem Lab Med 2014 Dec;52(12):1859-65

Background: CTNNA1 gene is a putative tumor suppressor for its roles in inhibiting proliferation and promoting apoptosis. Aberrant expression of CTNNA1 is regulated by epigenetic mechanisms including both promoter methylation and histone deacetylation in hematopoietic malignancies. However, the clinical relevance of CTNNA1 methylation remains rarely known in myelodysplastic syndrome (MDS). Read More

Leuk Res 2014 Mar 15;38(3):304-9. Epub 2013 Nov 15.

Department of Hematology, Hospital Universitario de Salamanca, Salamanca, Spain.

Patients with isolated del(5q) and MDS are considered to have good prognosis as compared to other MDS subtypes. Most patients suffered of anemia and 50% of them required transfusions at diagnosis. It is known that for patients with MDS and del(5q) in transfusion dependence(TD), Lenalidomide is the first choice treatment. Read More

Drugs 2013 Jul;73(11):1183-96

Adis, 41 Centorian Drive, Private Bag 65901, Mairangi Bay, North Shore, 0754, Auckland, New Zealand.

Lenalidomide (Revlimid(®)), a thalidomide analogue, is an orally administered second generation immunomodulator with anti-angiogenic, antineoplastic, anti-inflammatory and pro-erythropoietic properties. It is approved for the treatment of patients with transfusion-dependent anaemia due to International Prognostic Scoring System low- or intermediate-1-risk myelodysplastic syndrome (MDS) associated with either chromosome 5q deletion [del(5q)] with or without additional cytogenetic abnormalities (US, Japan and Switzerland etc.), or with an isolated del(5q) cytogenetic abnormality when other therapeutic options are insufficient or inadequate (EU) [featured indication]. Read More

Br J Haematol 2013 Jul 25;162(1):74-86. Epub 2013 Apr 25.

Laboratori de Citogenètica Molecular, Laboratori de Citologia Hematològica, Servei de Patologia, Hospital del Mar, Barcelona, Spain.

Lenalidomide is an effective drug in low-risk myelodysplastic syndromes (MDS) with isolated del(5q), although not all patients respond. Studies have suggested a role for TP53 mutations and karyotype complexity in disease progression and outcome. In order to assess the impact of complex karyotypes on treatment response and disease progression in 52 lenalidomide-treated patients with del(5q) MDS, conventional G-banding cytogenetics (CC), single nucleotide polymorphism array (SNP-A), and genomic sequencing methods were used. Read More

Eur J Haematol 2013 Jun 23;90(6):486-93. Epub 2013 Apr 23.

Hematology Division, Sixth Hospital Affiliated to Shanghai Jiaotong University, Shanghai, China.

Objectives: Haploinsufficiency of the ribosomal protein S14 (RPS14) has been identified as a causal factor in myelodysplastic syndrome (MDS) with isolated del (5q). This study was carried out to investigate RPS14 expression in MDS without 5q deletion and the role of lower expressed RPS14 plays in pathogenesis and the prognosis and lenalidomide-response predicting of non-5q-MDS.

Patients And Methods: The expression level of RPS14 transcription was detected in 156 MDS patients without 5q-. Read More

Eur J Haematol 2012 Dec 16;89(6):469-77. Epub 2012 Oct 16.

Department of Hematology, The Sixth Hospital, Shanghai Jiaotong University, Shanghai, China.

Objectives: Human Disabled-2 (Dab2), a putative tumor suppressor gene, is frequently down-regulated in human tumors. This study aims to explore the association between Dab2 methylation status and expression in newly diagnosed myelodysplastic syndrome (MDS) patients and patients who received 5-aza-2'-deoxycytidine (decitabine) treatment, so as to determine the effect of Dab2 in the pathogenesis of MDS.

Methods: Methylation-specific polymerase chain reaction and bisulfite sequencing were used to detect the methylation status of Dab2 gene. Read More

Genes Chromosomes Cancer 2012 Dec 30;51(12):1086-92. Epub 2012 Aug 30.

Laboratoire d'Hématologie, Hôpital Avicenne, Assistance Publique-Hôpitaux de Paris (AP-HP)/Université Paris 13, Bobigny. France.

TP53 mutations are frequent in myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) with complex karyotype that include del(5q) and are often associated with deletion of 17p. They have also recently been observed in MDS with isolated del(5q). We assessed the incidence of 17p deletion detected by fluorescence in situ hybridization (FISH) and of TP53 mutations detected by direct sequencing and their correlation and prognostic value in 26 MDS and 17 AML with del(5q). Read More

Clin Lymphoma Myeloma Leuk 2012 Oct 18;12(5):375-83. Epub 2012 May 18.

Institute of Hematology and Blood Transfusion, Prague, Czech Republic.

Unlabelled: We used microarray profiling to investigate the direct effects of lenalidomide on gene expression in isolated CD14(+) monocytes from 6 patients with del(5q). Our data demonstrate that changes in genes involved the tumor necrosis factor (TNF) signaling pathway and the bone marrow stroma, suggesting that treatment with lenalidomide may help restore the damaged niche and suppress the TNF signaling pathway.

Background: Lenalidomide is an effective treatment for patients with del(5q) and myelodysplastic syndrome (MDS) The exact mechanism of lenalidomide function and its impact on the prognosis of patients is not known exactly. Read More

Am J Hematol 2011 May;86(5):393-8

Department of Medicine, Division of Hematology, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA.

World Health Organization (WHO) criteria were used to identify 143 consecutive patients (median age 73 years; 90 females) with myeloid neoplasms and isolated del(5q) seen between 1989 and 2009. We have previously reported on 88 (61%) of these patients who met criteria for WHO defined "myelodysplastic syndromes (MDS) with isolated del(5q)." The remaining 55 patients were classified as having "other" MDS variants (n = 29; 20%), acute myeloid leukemia (AML; n = 14; 10%), or myeloproliferative neoplasms (MPN; n = 12; 8%). Read More

Cytometry B Clin Cytom 2011 May 23;80(3):150-7. Epub 2010 Dec 23.

Hematologics, Seattle, Washington, 98121, USA.

Background: In patients with unexplained cytopenias, abnormal karyotyping studies can be found with inconclusive light microscopic findings. Multidimensional flow cytometry (FCM) can identify myelomonocytic cells with aberrant phenotypes often not seen by standard morphology.

Methods: In 431 patients presenting with unexplained cytopenia(s) FCM results were compared to abnormal karyotyping and FISH results recognized as associated with myelodysplastic syndrome (MDS) in the 2008 WHO classification, to assess the degree of and types of phenotypic abnormalities observed using a previously reported flow cytometric scoring system (FCSS). Read More

J Hematol Oncol 2011 Jan 6;4. Epub 2011 Jan 6.

Department of Molecular Genetics, Institute of Hematology and Blood Transfusion, Prague, Czech Republic.

Background: Myelodysplastic syndrome with isolated chromosome 5q deletion (5q- syndrome) is a clonal stem cell disorder characterized by ineffective hematopoiesis. MicroRNAs (miRNAs) are important regulators of hematopoiesis and their aberrant expression was detected in some clonal hematopoietic disorders. We thus analyzed miRNA expressions in bone marrow CD34+ cells of 5q- syndrome patients. Read More

Pol J Pathol 2010 ;61(2):105-9

Mateusz Ziarkiewicz, Department of Haematology, Oncology and Internal Diseases, Warsaw Medical University, ul. Banacha 1a, 02-090 Warszawa.

Refractory anaemia with ringed sideroblasts associated with marked thrombocytosis (RARS-T) is a rare entity belonging to myeloproliferative/myelodysplastic syndromes. Myelodysplastic syndrome (MDS) with isolated del(5q) is a category of MDS characterized by better prognosis and specific morphology. Herein we describe a 69-year-old male with anaemia and thrombocytosis presenting with coexisting features of both these rare diseases. Read More

Am J Hematol 2010 Aug;85(8):609-10

Department of Histopathology, Hammersmith Hospital Campus, Imperial College Healthcare NHS Trust, London, United Kingdom.

Ann Biol Clin (Paris) 2010 Mar-Apr;68(2):248-53

Laboratoire d'hématologie, Hôpital Charles Foix, AP-HP, Ivry-sur-Seine.

We report two cases of myelodysplastic syndrome (MDS) with del(5q) isolated cytogenetic abnormality in elderly patients: AREB-1 in Patient 1, "5q syndrome" in Patient 2. A first line of treatment including hematopoietic growth factors (darbepoetin alone or associated with G-CSF) failed after several months and a treatment with lenalidomide was initiated in both cases. The treatment was poorly tolerated (myelosuppression) in Patient 1 without an improvement of the quality of life; a progression of the disease was observed with an increase of the bone marrow blastosis and a new acquired karyotypic abnormality (t13;17), leading to the prescription of 5-azacytidine. Read More

J Blood Med 2010 25;1:171-82. Epub 2010 Aug 25.

Department of Pathology, Mahatma Gandhi Medical College and Research Institute, Puducherry-607402, India.

The myelodysplastic Syndromes (MDS) are a group of clonal hematopoietic stem cell diseases characterized by cytopenia(s), dysplasia in one or more of the major myeloid cell lines, ineffective hematopoiesis, and increased risk of development of acute myeloid leukemia. The classification and the diagnostic criteria have been redefined by the recent World Health Organization Classification of Tumors - International Agency for Research on Cancer for Hematopoietic and Lymphoid Tissues. The myelodysplastic syndromes are now classified into the following categories - refractory cytopenia with unilineage dysplasia, refractory anemia with ring sideroblasts, refractory cytopenia with multilineage dysplasia, refractory anemia with excess blasts, myelodysplastic syndrome associated with isolated del (5q), myelodysplastic syndrome - unclassifiable, and childhood myelodysplastic syndrome. Read More

Oncogene 2009 Oct 13;28(39):3429-41. Epub 2009 Jul 13.

Laboratories of Cell Structure & Signal Integration, Van Andel Research Institute, Grand Rapids, MI 49503, USA.

Complete loss or interstitial deletions of chromosome 5 are the most common karyotypic abnormality in myelodysplastic syndromes (MDSs). Isolated del(5q)/5q- MDS patients have a more favorable prognosis than those with additional karyotypic defects, who tend to develop myeloproliferative neoplasms (MPNs) and acute myeloid leukemia. The frequency of unbalanced chromosome 5 deletions has led to the idea that 5q harbors one or more tumor-suppressor genes that have fundamental roles in the growth control of hematopoietic stem/progenitor cells (HSCs/HPCs). Read More

Leuk Lymphoma 2009 Aug;50(8):1333-5

Department of Pathology, Queen Elizabeth Hospital, Hong Kong SAR, China.

JAK2 V617F mutation is mostly seen in BCR-ABLI negative myeloproliferative neoplasms. Among other myeloid neoplasms, it occurs with remarkably high frequency in refractory anemia with ring sideroblasts associated with marked thrombocytosis, a group of myeloid neoplasms with both dysplastic and proliferative features. It has also been reported in occasional cases of myelodysplastic syndrome with isolated del(5q), often with a diagnosis of refractory cytopenia with multilineage dysplasia. Read More

Ann Hematol 2009 Dec 5;88(12):1207-13. Epub 2009 May 5.

Clinic for Stem Cell Transplantation, University Medical Center Hamburg (UCCH), Martinistr. 52, Hamburg 20246, Germany.

According to the new World Health Organization (WHO) classification (2008), chronic myeloid malignancies are divided in myeloproliferative neoplasms (MPN), myelodysplastic syndromes (MDS), and overlap MDS/MPN cases. From morphological aspects, these categories show overlaps. To evaluate whether these morphological similarities have genetic parallels, we investigated 1,851 cases with suspected/confirmed myelodysplastic or myeloproliferative diseases by chromosome banding and molecular analyses. Read More

Blood 2007 Dec;110(12):3825

Memorial Sloan Kettering Cancer Center, USA.

Genes Chromosomes Cancer 2007 Dec;46(12):1119-28

Institute of Human Genetics and Anthropology, Heinrich-Heine-University Duesseldorf, 40225 Duesseldorf, Germany.

Isolated deletions of the long arm of chromosome 5, del(5q), are observed in 10% of myelodysplastic syndromes (MDS) and are associated with a more favorable prognosis, although the clinical course varies considerably. If one or more additional chromosomal aberrations are present, this correlates with a significantly shorter overall survival. To assess the frequency of hidden abnormalities in cases with an isolated cytogenetic del(5q), we have performed a genome wide high resolution 44 K 60mer oligonucleotide array comparative genomic hybridization (aCGH) study using DNA from bone marrow cells of 12 MDS and one AML patient. Read More

Curr Treat Options Oncol 2007 Apr;8(2):117-28

Radhey Khanna MDS Center, Division of Hematology, University of Massachusetts Medical Center, 364 Plantation Street, Worcester, MA 01605, USA.

The heterogeneity of myelodysplastic syndromes (MDS) has driven the search for unifying biologic and clinical features that would stratify patients into distinct prognostic and therapeutic subgroups. Cytogenetics has been shown to impact the course of myelodysplasia. Despite the presence of non-random cytogenetic abnormalities in approximately 50% of MDS patients, it is significant that only a proportion of metaphases may contain the abnormality. Read More

Cancer Genet Cytogenet 2002 Oct;138(1):80-4

Laboratoire de Cytogénétique Onco-Hématologique, Hôpital Hôtel-Dieu, Paris, France.

The bone marrow karyotypes of three patients with acute myelocytic leukemia (AML) or myelodysplastic syndrome (MDS) were studied at diagnosis and revealed, multiple copies of the same chromosomal anomaly, considered as psu idic(21)(q22) associated with other rearrangement(s). The karyotype of a fourth patient with MDS in transformation showed one copy of a dicentric marker presumably derived from a similar psu idic(21) by (tandem?) interstitial amplification of part of its structure, resembling a "homogeneous staining region", and described as der(21)psu idic(21)(q22)hsr(21)(q22). This rearrangement, previously described in isolated cases only, might be considered as recurrent in AML/MDS and associated with an unfavorable prognosis. Read More

Leuk Res 1993 Nov;17(11):921-6

Service des Maladies du Sang, CHU, Lille, France.

We report on 8 cases of de novo myelodysplastic syndromes (MDS) with deletion of the long arm of chromosome 20 (del 20q), who represented about 2% (8/392) of our cases of de novo MDS with cytogenetic analysis seen during a period of 9 yr. Median age was 69 yr, and there were 7 males and 1 female. Anemia was absent or very mild (Hb > 11 g/dl) in 5 patients. Read More