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Haematologica 2019 Mar 4;104(3):497-504. Epub 2018 Oct 4.

Assistance Publique-Hôpitaux de Paris (AP-HP), Service d'Hématologie Biologique, Hôpitaux Universitaires Paris Centre, Institut Cochin, Université Paris Descartes.

Erythropoiesis-stimulating agents are generally the first line of treatment of anemia in patients with lower-risk myelodysplastic syndrome. We prospectively investigated the predictive value of somatic mutations, and biomarkers of ineffective erythropoiesis including the flow cytometry RED score, serum growth-differentiation factor-15, and hepcidin levels. Inclusion criteria were no prior treatment with erythropoiesis-stimulating agents, low- or intermediate-1-risk myelodysplastic syndrome according to the International Prognostic Scoring System, and a hemoglobin level <10 g/dL. Read More

Am J Clin Pathol 2017 Jul;148(1):49-57

Department of Pathology and Laboratory Medicine, Weill Cornell Medical College/New York Presbyterian Hospital, New York, NY.

Objectives: Three situations qualify as myelodysplastic syndrome, unclassifiable (MDS-U): (1) refractory cytopenia with dysplasia and 1% blasts in peripheral blood (BL), (2) pancytopenia with unilineage dysplasia (Pan), and (3) persistent cytopenia, less than 5% bone marrow blasts, and less than 10% dysplastic cells and presence of MDS-defining cytogenetic abnormalities (CG). We compared the clinicopathologic features and mutational profiles for these three groups.

Methods: MDS-U cases were reviewed at four major academic institutions. Read More

Cancer Biol Med 2016 Sep;13(3):360-372

Malignant Hematology Program, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL 33612, USA.

The myelodysplastic/myeloproliferative neoplasms (MDS/MPNs) are a unique group of hematologic malignancies characterized by concomitant myelodysplastic and myeloproliferative features. According to the 2008 WHO classification, the category includes atypical chronic myeloid leukemia (aCML), chronic myelomonocytic leukemia (CMML), juvenile myelomonocytic leukemia (JMML), MDS/MPN-unclassifiable (MDS/MPN-U), and the provisional entity refractory anemia with ring sideroblasts and thrombocytosis (RARS-T). Although diagnosis currently remains based on clinicopathologic features, the incorporation of next-generation platforms has allowed for the recent molecular characterization of these diseases which has revealed unique and complex mutational profiles that support their distinct biology and is anticipated to soon play an integral role in diagnosis, prognostication, and treatment. Read More

Leuk Lymphoma 2017 04 11;58(4):872-881. Epub 2016 Aug 11.

a Division of Hematology, Department of Internal Medicine , Mayo Clinic College of Medicine , Rochester , MN.

MDS/MPN (myelodysplastic syndrome/myeloproliferative neoplasm) overlap syndromes are myeloid malignancies for which allogeneic hematopoietic stem cell transplant (allo-HSCT) is potentially curative. We describe transplant outcomes of 43 patients - 35 with chronic myelomonocytic leukemia, CMML (of which 17 had blast transformation, BT) and eight with MDS/MPN-unclassifiable (MDS/MPN,U). At median follow-up of 21 months, overall survival (OS), cumulative incidence of relapse (CIR) and non-relapse mortality (NRM) were 55%, 29%, and 25% respectively in CMML without BT and 47%, 40%, and 34% respectively in CMML with BT. Read More

PLoS One 2016 18;11(7):e0158649. Epub 2016 Jul 18.

Greehey Children's Cancer Research Institute, University of Texas Health Science Center at San Antonio (UTHSCSA), San Antonio, TX, United States of America.

Perturbations in CREB binding protein (CREBBP) are associated with hematopoietic malignancies, including myelodysplastic syndrome (MDS). Mice hemizygous for Crebbp develop myelodysplasia with proliferative features, reminiscent of human MDS/myeloproliferative neoplasm-unclassifiable (MDS/MPN-U), and a proportion goes on to develop acute myeloid leukemia (AML). We have also shown that the Crebbp+/- non-hematopoietic bone marrow microenvironment induces excessive myeloproliferation of wild-type cells. Read More

Genes Chromosomes Cancer 2016 11 4;55(11):847-54. Epub 2016 Jul 4.

Faculty of Medicine, Department of Laboratory Medicine Lund, Division of Clinical Genetics, Lund University, Lund, Sweden.

Myelodysplastic/myeloproliferative neoplasms, unclassifiable (MDS/MPN-U) are rare genetically heterogeneous hematologic diseases associated with older age and a poor prognosis. If the disease progresses into acute myeloid leukemia (AML), it is often refractory to treatment. To gain insight into genetic alterations associated with disease progression, whole exome sequencing and single nucleotide polymorphism arrays were used to characterize the bone marrow and blood samples from a 39-year-old woman at MDS/MPN-U diagnosis and at AML progression, in which routine genetic diagnostics had not identified any genetic alterations. Read More

Indian J Pathol Microbiol 2016 Jan-Mar;59(1):133-4

Department of Hematology, N.R.S. Medical College, Kolkata, West Bengal, India.

Rinsho Ketsueki 2015 Jul;56(7):877-82

Department of Hematology, Juntendo University Graduate School of Medicine.

To investigate the current situation and issues regarding the diagnosis of Philadelphia-negative myeloproliferative neoplasms (MPN) in Japan, we retrospectively analyzed an accumulated cohort consisting of 1,081 patients with suspected MPN. Based on WHO2008 diagnostic criteria, we diagnosed 101 of these patients with polycythemia vera, 179 with essential thrombocythemia, 36 with primary myelofibrosis, 45 with unclassifiable MPN, and 4 with myelodysplastic syndromes. Out of 716 patients, 235 were not diagnosed with MPN despite the detection of a JAK2, CALR, or MPL mutation. Read More

Cytometry B Clin Cytom 2015 Jul-Aug;88(4):236-43. Epub 2014 Dec 30.

Department of Hematopathology, the University of Texas MD Anderson Cancer Center, Houston, Texas.

Background: Compared with the proven utility of flow cytometry immunophenotyping (FCI) analysis in the workup of myelodysplastic syndromes (MDS), immunophenotypic alterations in myeloproliferative neoplasms (MPN) have been less studied and the potential utility of FCI is not defined.

Methods: Bone marrow (BM) samples of 83 Philadelphia-negative MPN patients were assessed by multicolor FCI including 27 with essential thrombocythemia (ET); 17 polycythemia vera (PV); 33 primary myelofibrosis (PMF) and 6 MPN-unclassifiable (MPN-U). The time interval from initial diagnosis of MPN to FCI analysis was 18 months (0-370). Read More

Acta Med Okayama 2014 Dec;68(6):363-8

Department of Internal Medicine, Himeji St. Mary's Hospital, Himeji, Hyogo 670-0801,

Leukocytosis is occasionally seen in patients with presumptive but undiagnosed myeloproliferative disorders (MPD). A 74-year-old woman was admitted to our hospital for tarry stools, anemia, and marked peripheral leukocytosis of 1.4×10(5)/μL. Read More

Cytometry B Clin Cytom 2014 Dec 11. Epub 2014 Dec 11.

Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA; Department of Laboratory Medicine, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, China.

Background: Compared with the proven utility of flow cytometry immunophenotyping (FCI) analysis in the workup of myelodysplastic syndromes (MDS), immunophenotypic alterations in myeloproliferative neoplasms (MPN) have been less studied and the potential utility of FCI is not defined. Methods: Bone marrow (BM) samples of 83 Philadelphia-negative MPN patients were assessed by multicolor FCI including 27 with essential thrombocythemia (ET); 17 polycythemia vera (PV); 33 primary myelofibrosis (PMF) and 6 MPN-unclassifiable (MPN-U). The time interval from initial diagnosis of MPN to FCI analysis was 18 months (0-370). Read More

Ann Hematol 2015 Apr 13;94(4):565-73. Epub 2014 Nov 13.

Department of Hematology, Hospital General Universitario Gregorio Marañon, C/ Doctor Esquerdo 46, 28007, Madrid, Spain,

Previous studies have shown the reproducibility of the 2008 World Health Organization (WHO) classification in myelodysplastic syndromes (MDS), especially when multilineage dysplasia or excess of blasts are present. However, there are few data regarding the reproducibility of MDS with unilineage dysplasia. The revised International Prognostic Scoring System R-IPSS described two new morphological categories, distinguishing bone marrow (BM) blast cell count between 0-2 % and >2- < 5 %. Read More

Curr Hematol Malig Rep 2014 Dec;9(4):400-6

Leukemia Program, Cleveland Clinic Taussig Cancer Institute, Desk R35, 9500 Euclid Avenue, Cleveland, OH, 44195, USA,

Patients with the myelodysplastic syndromes/myeloproliferative neoplasm (MDS/MPN) overlap, including chronic myelomonocytic leukemia (CMML), atypical chronic myeloid leukemia (aCML), MDS/MPN-unclassifiable (MDS/MPN-U), and refractory anemia with ring sideroblasts associated with marked thrombocytosis (RARS-T), often present with findings of both dysplasia and marrow proliferation, occupying the border region of two seemingly divergent camps. Historically, these disorders which have been lumped with either MDS or MPN have represented a minority, or been excluded all together, from the development of prognostic models and clinical trials. Therefore, Food and Drug Administration approved therapies specifically for overlap subtypes are lacking. Read More

Rinsho Ketsueki 2014 04;55(4):440-4

Department of Gastroenterology and Hematology/Clinical Oncology, Internal Medicine, Steel Memorial Muroran Hospital.

A 79-year-old man had been followed up since July 2003 based on a diagnosis of essential thrombocythemia (ET). The patient visited our hospital after developing a high fever and rash in August 2010, and Sweet's syndrome was diagnosed based on skin biopsy results. The bone marrow aspirate showed features like those of myelodysplastic/myeloproliferative neoplasm (MDS/MPN, unclassifiable). Read More

Int J Lab Hematol 2015 Apr 21;37(2):181-9. Epub 2014 May 21.

Department of Laboratory Medicine, Ewha Womans University School of Medicine, Seoul, South Korea; Department of Laboratory Medicine, Eone Laboratories, Incheon, South Korea.

Introduction: Myeloproliferative neoplasms (MPN) and myelodysplastic/myeloproliferative neoplasms (MDS/MPN) may transform into secondary myelofibrosis (MF) or evolve into acute myeloid leukemia (AML). The genetic mechanisms underlying disease progression in MPN and MDS/MPN patients remain unclear. The purpose of this study was to investigate sequential genomic aberrations identified by single nucleotide polymorphism array (SNP-A)-based karyotyping that can detect cryptic aberrations or copy neutral loss of heterozygosity (CN-LOH) in the chronic phase and during disease progression of MPN and MDS/MPN patients. Read More

Blood 2014 Apr 13;123(17):2645-51. Epub 2014 Mar 13.

Department of Hematopathology, The University of Texas M.D. Anderson Cancer Center, Houston, TX;

Atypical chronic myeloid leukemia (aCML) is a rare subtype of myelodysplastic/myeloproliferative neoplasm (MDS/MPN) largely defined morphologically. It is, unclear, however, whether aCML-associated features are distinctive enough to allow its separation from unclassifiable MDS/MPN (MDS/MPN-U). To study these 2 rare entities, 134 patient archives were collected from 7 large medical centers, of which 65 (49%) cases were further classified as aCML and the remaining 69 (51%) as MDS/MPN-U. Read More

Rom J Morphol Embryol 2013 ;54(4):1177-82

Center of Hematology and Bone Marrow Transplantation, "Fundeni" Clinical Institute, "Carol Davila" University of Medicine and Pharmacy, Bucharest, Romania;

In the WHO classification, there is a provisional entity called Myelodysplastic/Myeloproliferative Neoplasm, Unclassifiable (MDS/MPN, U). Refractory anemia with ringed sideroblasts associated with marked thrombocytosis (RARS-T) was included in this category. Recently published studies report a small percentage of patients with RARS-T. Read More

Curr Opin Hematol 2014 Mar;21(2):131-40

aDepartment of Translational Hematology and Oncology Research bCleveland Clinic Taussig Cancer Institute cLeukemia Program, Department of Hematologic Oncology and Blood Disorders, Taussig Cancer Institute, Cleveland Clinic, Cleveland, Ohio, USA *Both authors contributed equally to the writing of this article.

Purpose Of Review: Myelodysplastic/myeloproliferative neoplasms (MDS/MPNs), including chronic myelomonocytic leukemia, atypical chronic myeloid leukemia, MDS/MPN-Unclassifiable, ring sideroblasts associated with marked thrombocytosis, and juvenile myelomonocytic leukemia, are clonal hematologic diseases characterized by myeloid dysplasia, proliferation, and absence of the molecular lesions BCR/ABL, PDGFRA, PDGFRB, and FGFR1. There are currently no US Food and Drug Administration approved therapies for all MDS/MPN subtypes. Advances in the understanding of the biologic and molecular drivers of these diseases will help in diagnosis, prognosis, and therapeutics. Read More

Am J Clin Pathol 2013 Sep;140(3):370-8

Department of Hematopathology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Unit 072, Houston, TX 77030, USA.

Objectives: To assess CD105 (endoglin) expression in 119 acute myeloid leukemia (AML) and 13 control cases using immunohistochemistry.

Methods: CD105 expression was assessed retrospectively by using immunohistochemistry in bone marrow specimens.

Results: CD105 was strongly and diffusely positive in all 9 (100%) AMLs with t(15;17)(q24. Read More

J Clin Oncol 2013 Jul 24;31(21):2662-70. Epub 2013 Jun 24.

Dana-Farber Cancer Institute, D1B05, 450 Brookline Ave, Boston, MA 02215, USA.

Purpose: Myelodysplastic syndromes (MDS) are clonal hematopoietic disorders that are more common in patients aged ≥ 60 years and are incurable with conventional therapies. Reduced-intensity conditioning (RIC) allogeneic hematopoietic stem-cell transplantation is potentially curative but has additional mortality risk. We evaluated RIC transplantation versus nontransplantation therapies in older patients with MDS stratified by International Prognostic Scoring System (IPSS) risk. Read More

Leukemia 2013 Sep 30;27(9):1852-60. Epub 2013 Apr 30.

MLL Munich Leukemia Laboratory, Munich, Germany.

Chronic myeloid malignancies are categorized to the three main categories myeloproliferative neoplasms (MPNs), myelodysplastic syndromes (MDSs) and MDS/MPN overlap. So far, no specific genetic alteration profiles have been identified in the MDS/MPN overlap category. Recent studies identified mutations in SET-binding protein 1 (SETBP1) as novel marker in myeloid malignancies, especially in atypical chronic myeloid leukemia (aCML) and related diseases. Read More

Ann Biol Clin (Paris) 2013 Mar-Apr;71(2):139-44

Laboratoire d'hématologie, CHU Farhat Hached, Sousse, Tunisia.

Myelodysplastic syndromes (MDS) are myeloid disorders with various clinical and biological presentations. The French-American-British (FAB-1982) classification included five categories basing on morphology and bone marrow blast count. Three criteria are taken into account: 1) the percentage of blasts in peripheral blood and bone marrow, 2) the percentage of ringed sideroblasts, and 3) the number of monocytes in peripheral blood. Read More

Maedica (Buchar) 2012 Jun;7(2):173-6

Department of Hematology, Coltea Clinical Hospital, Bucharest, Romania.

The most recent WHO Classification of Tumors of Haematopoietic and Lymphoid Tissues describes a set of diseases framed as the MDS / MPN (myelodysplastic / chronic myeloproliferative syndromes). There are four subtypes comprised in this category: chronic myelomonocytic leukemia, juvenile myelomonocytic leukemia, atypical chronic myeloid leukemia and unclassifiable MDS / MPN. They combine both myelodysplastic and myeloproliferative features. Read More

Cytometry B Clin Cytom 2013 May 2;84(3):194-7. Epub 2013 Jan 2.

MLL Munich Leukemia Laboratory, Munich 81377, Germany.

Background: Within the myelodysplastic/myeloproliferative neoplasm (MDS/MPN) category of the WHO (2008), only chronic myelomonocytic leukemia was so far evaluated by multiparameter flow cytometry (MFC).

Methods: To investigate the potential of MFC for MDS/MPNs, unclassifiable (MDS/MPNu), and refractory anemia associated with ring sideroblasts and marked thrombocytosis (RARS-T), we studied 91 patients with these entities (60 males/31 females; 35.3-87. Read More

Leuk Res 2013 Jan 31;37(1):64-70. Epub 2012 Oct 31.

Department of Hematology, Oncology and Clinical Immunology, Heinrich-Heine-University, Düsseldorf, Germany.

In 2008, the WHO proposed changes in the classification of MDS regarding RCUD and MDS unclassifiable. We validated these proposals by using 2032 patients of the Düsseldorf MDS Registry. 10% of the patients had RCUD and 6% MDS-U. Read More

Rinsho Ketsueki 2012 Jun;53(6):618-22

Department of Hematology, Osaka City General Hospital.

A 61-year-old man was referred to our hospital for leukocytosis and thrombocytopenia. Bone marrow examination showed hypercellular bone marrow accompanied by dysplasia, and the karyotype of his bone marrow cells was 46,XY, der(5;12)(q10;q10), +mar,inc[3]/46,XY[12]. A diagnosis of myelodysplastic syndrome, unclassifiable, was made. Read More

Semin Diagn Pathol 2011 Nov;28(4):283-97

Department of Pathology, Hematopathology Section, University of Chicago, Chicago, Illinois, USA.

The myelodysplastic/myeloproliferative neoplasms (MDS/MPN) include clonal myeloid neoplasms that overlap the MDS and MPN categories and at the time of initial diagnosis exhibit some clinical, laboratory, or morphologic features supporting the diagnosis of myelodysplastic syndrome (MDS) and at the same time show proliferative features in keeping with the diagnosis of a myeloproliferative neoplasm (MPN). Although the clinical, morphologic, and laboratory findings vary along a continuum from MDS to MPN, distinctive features are usually present that allow assignment of most of the cases to 1 of 3 distinct subtypes recognized by the 2008 World Health Organization (WHO) classification: chronic myelomonocytic leukemia (CMML), atypical chronic myeloid leukemia, BCR-ABL(-)(aCML, BCR-ABL1(-)), and juvenile myelomonocytic leukemia (JMML). The WHO classification also recognizes a provisional category of the MDS/MPN, unclassifiable (MDS/MPN, U), including the provisional entity of refractory anemia with ring sideroblasts and thrombocytosis (RARS-T). Read More

Hematology Am Soc Hematol Educ Program 2011 ;2011:264-72

Department of Hematology Oncology, University of Pavia Medical School and Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.

According to the World Health Organization (WHO) classification of tumors of hematopoietic and lymphoid tissues, myelodysplastic/myeloproliferative neoplasms are clonal myeloid neoplasms that have some clinical, laboratory, or morphologic findings that support a diagnosis of myelodysplastic syndrome, and other findings that are more consistent with myeloproliferative neoplasms. These disorders include chronic myelomonocytic leukemia, atypical chronic myeloid leukemia (BCR-ABL1 negative), juvenile myelomonocytic leukemia, and myelodysplastic/myeloproliferative neoplasms, unclassifiable. The best characterized of these latter unclassifiable conditions is the provisional entity defined as refractory anemia with ring sideroblasts associated with marked thrombocytosis. Read More

Leukemia 2012 Jan 28;26(1):101-5. Epub 2011 Oct 28.

Division of Hematology, Department of Medicine, Mayo Clinic, Rochester, MN 55905, USA.

Unlike the case with acute myeloid leukemia, there is limited information on the prognostic impact of isocitrate dehydrogenase (IDH) mutations in myelodysplastic syndromes (MDS). In the current study of 277 patients with MDS, IDH mutations were detected in 34 (12%) cases: 26 IDH2 (all R140Q) and 8 IDH1 (6 R132S and 2 R132C). Mutational frequency was 4% (2 of 56) in refractory anemia with ring sideroblasts, 12% (16 of 130) in refractory cytopenia with multilineage dysplasia, 14% (2 of 14) in MDS-unclassifiable, 14% (6 of 42) in refractory anemia with excess blasts (RAEB)-1 and 23% (8 of 35) in RAEB-2. Read More

Haematologica 2012 Feb 11;97(2):206-12. Epub 2011 Oct 11.

Department for Haematology, Oncology and Clinical Immunology, University of Duesseldorf Medical Faculty, Duesseldorf, Germany.

Background: Few data are available on therapy-related myelodysplastic syndromes and acute myeloid leukemia developing after radioiodine treatment.

Design And Methods: We retrospectively analyzed 39 patients with myeloid neoplasms following radioiodine treatment, whose data were reported to the Duesseldorf Myelodysplastic Syndromes Register (8 of 3814 patients) and five other German Myelodysplastic Syndromes centers (n=31) between 1982 and 2011. These data were compared with those from 165 patients from our Myelodysplastic Syndromes Register with therapy-related myeloid neoplasms following chemotherapy (n=90), radiation (n=30), or radiochemotherapy (n=45). Read More

Mod Pathol 2011 Mar 19;24(3):375-83. Epub 2010 Nov 19.

Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030-4009, USA.

Pure erythroid leukemia (PEL) is rare, characterized by a neoplastic proliferation of erythroblasts. Given recent incorporation of molecular genetic findings and clinical features in the revised 2008 World Health Organization classification scheme of acute myeloid leukemia, we questioned if PEL still remains as a distinct subtype of acute myeloid leukemia. In this retrospective study, we identified 18 cases of acute leukemia with morphologic and immunophenotypic features of PEL. Read More

Int J Lab Hematol 2010 Dec;32(6 Pt 2):559-71

Department of Pathology, University of New Mexico, Albuquerque, NM 87102, USA.

Introduction: The 2008 World Health Organization classification of myeloid neoplasms includes the diagnostic category, myelodysplastic/myeloproliferative neoplasms (MDS/MPN), which encompasses those rare clonal myeloid proliferations that at initial presentation, show overlapping myeloproliferative and myelodysplastic features, making classification as either a myelodysplastic syndrome (MDS) or myeloproliferative neoplasm (MPN) problematic. There are four main subcategories, chronic myelomonocytic leukemia (CMML), atypical chronic myeloid leukemia, BCR-ABL1-negative (aCML), juvenile myelomonocytic leukemia (JMML), and myelodysplastic/myeloproliferative neoplasm, unclassifiable (MDS/MPN-U), which also includes the provisional entity, refractory anemia with ring sideroblasts associated with marked thrombocytosis (RARS-T). Notably, the morphological features typical of MDS/MPNs are not specific and can be seen in other myeloid neoplasms at presentation or as part of disease progression or transformation. Read More

Ann Hematol 2011 Apr 22;90(4):469-71. Epub 2010 Jun 22.

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

Chem Biol Interact 2010 Mar 24;184(1-2):30-8. Epub 2009 Nov 24.

Fudan-Cinpathogen Clinical and Molecular Research Center, Institutes of Biomedical Sciences, Fudan University, Shanghai, China.

We characterized the prevalence of hematopoietic and lymphoid disease for 2923 consecutive patients presenting at 29 hospitals from August 2003 to June 2007. Diagnoses were made in our laboratory using WHO criteria based on morphologic, immunophenotypic, cytogenetic, FISH and molecular data. A total of 611 subjects (322 males/289 females) were prospectively diagnosed with MDS using WHO (2001) criteria. Read More

Nat Rev Clin Oncol 2009 Nov 6;6(11):627-37. Epub 2009 Oct 6.

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

The 2008 WHO classification system for hematological malignancies is comprehensive and includes histology and genetic information. Myeloid neoplasms are now classified into five categories: acute myeloid leukemia, myelodysplastic syndromes (MDS), myeloproliferative neoplasms (MPN), MDS/MPN, and myeloid and/or lymphoid malignancies associated with eosinophilia and PDGFR or FGFR1 rearrangements. MPN are subclassified into eight separate entities: chronic myelogenous leukemia, polycythemia vera, essential thrombocythemia, primary myelofibrosis, systemic mastocytosis, chronic eosinophilic leukemia not otherwise specified, chronic neutrophilic leukemia, and unclassifiable MPN. Read More

Cancer 2009 Sep;115(17):3842-7

Department of Medicine, Mayo Clinic, Rochester, Minnesota, USA.

The first formal classification of chronic myeloid neoplasms is credited to William Dameshek, who in 1951 described the concept of "myeloproliferative disorders (MPD)" by grouping together chronic myelogenous leukemia, polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF). The 2001 World Health Organization (WHO) classification of myeloid malignancies included these MPDs under the broader category of chronic myeloproliferative diseases (CMPD), which also included chronic neutrophilic leukemia, chronic eosinophilic leukemia/hypereosinophilic syndrome (CEL/HES), and "CMPD, unclassifiable." The revised 2008 WHO classification system featured the following changes: 1) the term "CMPD" was replaced by "myeloproliferative neoplasm (MPN)," 2) mast cell disease was formally included under the category of MPN, and 3) the subcategory of CEL/HES was reorganized into "CEL not otherwise specified (CEL-NOS)" and "myeloid and lymphoid neoplasms with eosinophilia and abnormalities of PDGFRA, PDGFRB, and FGFR1"; CEL-NOS remained a subcategory of "MPN," whereas the latter neoplasms were now assigned a new category of their own. Read More

Biol Blood Marrow Transplant 2009 Jan;15(1):30-8

Blood and Marrow Transplant Program, Departments of Medicine and Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, Minnesota 55455, USA.

Allogeneic stem cell transplantation is the only known curative therapy for myelodysplastic syndromes (MDS). We present the transplant outcomes for 84 adult MDS patients, median age 50 (18-69 years), undergoing allogeneic hematopoietic stem cell transplantation (HSCT) at the University of Minnesota between 1995 and 2007. By WHO criteria 35 (42%) had refractory anemia with excess blasts (RAEB-1 or 2), 23 (27%) had refractory cytopenia with multilineage dysplasia (RCMD) or RCMD and ringed sideroblasts (RCMD-RS), and the remaining 26 (31%) had refractory anemia (RA), myelodysplastic syndrome-unclassifiable (MDS-U), chronic myelomonocytic leukemia (CMML), myelodysplastic/myeloproliferative disease (MDS/MPD), or myelodysplastic syndrome-not otherwise specified (MDS-NOS). Read More

Cancer Res 2008 Dec;68(24):10349-57

Department of Hematologic Oncology and Blood Disorders, Experimental Hematology and Hematopoiesis Section, Taussig Cancer Center, Cleveland Clinic, Cleveland, Ohio 44195, USA.

Two types of acquired loss of heterozygosity are possible in cancer: deletions and copy-neutral uniparental disomy (UPD). Conventionally, copy number losses are identified using metaphase cytogenetics, whereas detection of UPD is accomplished by microsatellite and copy number analysis and as such, is not often used clinically. Recently, introduction of single nucleotide polymorphism (SNP) microarrays has allowed for the systematic and sensitive detection of UPD in hematologic malignancies and other cancers. Read More

Zhonghua Nei Ke Za Zhi 2008 Jun;47(6):464-7

Hematology Department, Huashan Hospital, Fudan University, Shanghai 200040, China.

Objective: To investigate the WHO classification and cytogenetic characteristics of primary myelodysplastic syndrome (MDS) in adults of Shanghai area and then compare them with those of western countries.

Methods: The consecutive samples of 435 patients with MDS in Sino-US Shanghai Leukemia Cooperative Group were collected prospectively and diagnosed with WHO classification. Cytogenetic analysis was performed using chromosome G-banding and fluorescence in situ hybridization (FISH) techniques. Read More

Leukemia 2008 Jul 15;22(7):1308-19. Epub 2008 May 15.

Department of Pathology and Laboratory Medicine, Clarian Pathology Laboratory, Indiana University School of Medicine, Indianapolis, IN 46202, USA.

The 2001 World Health Organization (WHO)-sponsored classification of hematopoietic tumors has, for the first time, clearly defined a group of rare myeloid neoplasms termed myelodysplastic/myeloproliferative diseases (MDS/MPDs). This group includes three main entities, chronic myelomonocytic leukemia, atypical chronic myeloid leukemia and juvenile myelomonocytic leukemia, and also several less well defined, 'unclassifiable' disorders with MDS/MPN-like features. In the upcoming fourth edition of the WHO fascicle, due out later this year, the term 'MPD' is replaced by 'myeloproliferative neoplasm (MPN)'. Read More

Leukemia 2008 Jun 6;22(6):1295-8. Epub 2007 Dec 6.

Mod Pathol 2007 Sep 20;20(9):929-35. Epub 2007 Jul 20.

Department of Pathology and Laboratory Medicine, The Methodist Hospital and the Methodist Hospital Research Institute, Houston, TX 77030, USA.

Extramedullary hematopoiesis (EMH) in the spleen is a characteristic feature of the chronic myeloproliferative disorders (CMPDs) and various other neoplastic or reactive myeloid conditions. However, the origin of these hematopoietic precursor cells and the molecular mechanisms underlying their development in the spleen is uncertain. The V617F mutation in the Janus Kinase 2 gene (JAK2(V617F)) was recently shown to be frequently and preferentially present in the peripheral blood and bone marrow cells of CMPD patients, and the resulting dysregulation of its downstream targets is important to CMPD pathogenesis. Read More

Blood 2007 Feb;109(3):1334-5

Am J Hematol 2006 Oct;81(10):779-86

University of Arizona Cancer Center, Tucson, Arizona 85724, USA.

A Native American-Indian female presenting with anemia and thrombocytosis was diagnosed with myelodysplastic syndrome (MDS, refractory anemia). Over the course of 5 years she developed cytopenias and periods of leukocytosis with normal bone marrow (BM) blast counts, features of an unclassifiable MDS/MPS syndrome. The patient ultimately progressed to acute myelogenous leukemia (AML, FAB M2) and had a normal karyotype throughout her course. Read More

Haematologica 2006 May;91(5):719-20

The JAK2/V617F mutation has been noted in essential thrombocytemia. We investigated 19 cases with refractory anemia with ringed sideroblasts (RARS), including three RARS with thrombocytosis (RARS-T). Only the RARS-T patients showed this mutation. Read More

Rinsho Byori 2006 Mar;54(3):243-9

Department of Medicine, Asahikawa City Hospital, Asahikawa 070-8610.

The WHO classification published in 2001 defined a new category of hematological disease, myelodysplastic/myeloproliferative diseases (MDS/MPD), that have both myelodysplasia and myeloproliferation at the time of initial presentation. This category consists of four subclasses, chronic myelomonocytic leukemia (CMML), atypical CML(aCML), juvenile chronic myelogenous leukemia and MDS/MPD-unclassifiable (MDS/MPD-u). In order to clarify the clinical features of these diseases, we analyzed clinical data of tentatively diagnosed MDS/MPD cases in the past ten years accumulated from affiliated hospitals. Read More

Leuk Res 2005 Apr 2;29(4):365-70. Epub 2004 Dec 2.

Service of Hematology, Consorcio Hospital General Universitario of Valencia, Spain.

Myelodysplastic syndromes (MDS) show occasionally thrombocytosis, common feature of myeloproliferative diseases (MPD), with the overlapping of both disorders. Classically, thrombocytosis has been associated with some MDS subtypes: refractory anaemia with ringed sideroblasts (RARS), 5q- syndrome and those MDS with 3q chromosome rearrangements. The recent WHO classification recognises an unclassifiable MDS/MPD category including some of these disorders. Read More

Pediatr Blood Cancer 2005 Mar;44(3):240-4

Department of Pathology, Louisiana State University School of Medicine, New Orleans, Louisiana, USA.

Background: The category, cytology, cytogenetics (CCC) system for myelodysplastic syndrome (MDS) and the pediatric WHO system for MDS/myeloproliferative disorder (MPD) have recently been proposed to characterize these diseases in pediatrics.

Objective: We compare the CCC and pediatric WHO systems against each other and against the French, American, British (FAB) and adult WHO classifications in order to determine which more accurately classifies these diseases and predicts outcome.

Methods: An 18-year retrospective review identified patients less than 18 years of age meeting CCC and/or pediatric WHO criteria for the diagnosis of MDS or MPD. Read More

Cancer Genet Cytogenet 2004 Sep;153(2):183-4