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Int J Lab Hematol 2022 May 24. Epub 2022 May 24.

Department of Laboratory Medicine, Yale School of Medicine, New Haven, Connecticut, USA.

Introduction: Recent data suggest basophils can adopt an atypical appearance in myeloid disorders including myeloproliferative neoplasms (MPNs) and myeloproliferative/myelodysplastic disease. We hypothesized that automated analysers may not accurately quantitate basophils in myeloid neoplasms based on scatter properties. This study examined basophil counts and properties in myeloid disorders by automated cell analyser, manual differential, and flow cytometry. Read More

Clin Lab 2022 Apr;68(4)

Background: Myelodysplastic/myeloproliferative neoplasm with ring sideroblasts and thrombocytosis (MDS/ MPN-RS-T) was newly introduced as a full entity in the 2016 revision of the WHO classification. In this study, we investigated the morphologic, laboratory, and clinical features of MDS/MPN-RS-T.

Methods: We reviewed the bone marrow and genetic studies of patients whose diagnoses were coded as "refractory anemia with ring sideroblasts (RARS)" or "MDS/MPN, unclassifiable" between January 2008 and April 2018. Read More

Cytogenet Genome Res 2021 17;161(12):564-568. Epub 2022 Jan 17.

Laboratory Medicine Program, University Health Network, and Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada.

Myelodysplastic/myeloproliferative neoplasm, unclassifiable (MDS/MPN-U) is a poorly characterized entity among overlap myeloid syndromes. Recent studies have shown heterogeneous mutational profiles in this group being able to subclassify them into entities closely related to the more well-established disorders under the umbrella term of the MDS/MPN group. Recurrent cytogenetic alterations are, nonetheless, rare in MDS/MPN-U. Read More

Front Oncol 2021 16;11:778741. Epub 2021 Nov 16.

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

The WHO-category Myelodysplastic/Myeloproliferative neoplasms (MDS/MPNs) recognizes a unique group of clonal myeloid malignancies exhibiting overlapping features of myelodysplastic as well as myeloproliferative neoplasms. The group consists of chronic myelomonocytic leukemia (CMML), atypical chronic myeloid leukemia, -negative (aCML), juvenile myelomonocytic leukemia (JMML), myelodysplastic/myeloproliferative neoplasm with ringed sideroblasts and thrombocytosis (MDS/MPN-RS-T), and myelodysplastic/myeloproliferative neoplasms, unclassifiable (MDS/MPN-U). The most frequent entity in this category is CMML, while all other diseases are extremely rare. Read More

J Int Med Res 2021 May;49(5):3000605211018426

The First Hospital of Jilin University, Changchun, China.

Myelodysplastic/myeloproliferative neoplasms (MDS/MPNs) are a heterogeneous group of hematologic malignancies characterized by dysplastic and myeloproliferative overlapping features in the bone marrow and blood. The occurrence of the disease is related to age, prior history of MPN or MDS, and recent cytotoxic or growth factor therapy, but it rarely develops after acute myeloid leukemia (AML). We report a rare case of a patient diagnosed with AML with t(8; 21)(q22; q22) who received systematic chemotherapy. Read More

Hematology Am Soc Hematol Educ Program 2020 12;2020(1):450-459

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

Myelodysplastic syndrome (MDS)/myeloproliferative neoplasm (MPN) overlap syndromes are uniquely classified neoplasms occurring in both children and adults. This category consists of 5 neoplastic subtypes: chronic myelomonocytic leukemia (CMML), juvenile myelomonocytic leukemia (JMML), BCR-ABL1-negative atypical chronic myeloid leukemia (aCML), MDS/MPN-ring sideroblasts and thrombocytosis (MDS/MPN-RS-T), and MDS/MPN-unclassifiable (U). Cytogenetic abnormalities and somatic copy number variations are uncommon; however, >90% patients harbor gene mutations. Read More

Hematology Am Soc Hematol Educ Program 2020 12;2020(1):460-464

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

Myelodysplastic syndrome (MDS)/myeloproliferative neoplasm (MPN) overlap syndromes are unique myeloid neoplasms, with overlapping features of MDS and MPN. They consist of four adult onset entities including chronic myelomonocytic leukemia (CMML), MDS/MPN-ring sideroblasts-thrombocytosis (MDS/MPN-RS-T), BCR-ABL1 negative atypical chronic myeloid leukemia (aCML) and MDS/MPN-unclassifiable (MDS/MPN-U); with juvenile myelomonocytic leukemia (JMML) being the only pediatric onset entity. Among these overlap neoplasms, CMML is the most frequent and is hallmarked by the presence of sustained peripheral blood monocytosis with recurrent mutations involving TET2 (60%), SRSF2 (50%) and ASXL1 (40%); with RAS pathway mutations and JAK2V617F being relatively enriched in proliferative CMML subtypes (WBC ≥13 × 109/L). Read More

Front Oncol 2020 7;10:579221. Epub 2020 Oct 7.

Department of Hematology, Peking Union Medical College Hospital, Chinese Academy of Medical Science, Beijing, China.

Dysplasia and proliferation are histological properties that can be used to diagnose and categorize myeloid tumors in myelodysplastic syndromes (MDS) and myeloproliferative neoplasms (MPN). However, these conditions are not exclusive, and overlap between them leads to another classification, MDS/MPN. As well as phenotype continuity, these three conditions may have genetic relationships that have not yet been identified. Read More

Blood Adv 2020 10;4(20):5285-5296

Laboratori de Citologia Hematològica, Servei de Patologia, Grup de Recerca Translacional en Neoplàsies Hematològiques (GRETNHE), and.

Oligomonocytic chronic myelomonocytic leukemia (OM-CMML) is defined as those myelodysplastic syndromes (MDSs) or myelodysplastic/myeloproliferative neoplasms, unclassifiable with relative monocytosis (≥10% monocytes) and a monocyte count of 0.5 to <1 × 109/L. These patients show clinical and genomic features similar to those of overt chronic myelomonocytic leukemia (CMML), although most of them are currently categorized as MDS, according to the World Health Organization 2017 classification. Read More

Best Pract Res Clin Haematol 2020 09 5;33(3):101195. Epub 2020 Jul 5.

Malignant Hematology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA. Electronic address:

The myelodysplastic/myeloproliferative neoplasms (MDS/MPN) are a heterogenous group of myeloid malignancies hallmarked by clinicopathologic features that overlap with myelodysplastic syndromes and myeloproliferative neoplasms. Formally recognized by the World Health Organization, this group includes the entities chronic myelomonocytic leukemia, juvenile myelomonocytic leukemia, atypical chronic myeloid leukemia, MDS/MPN with ring sideroblasts and thrombocytosis and MDS/MPN, unclassifiable. Advancements in next generation sequencing have begun to unravel the molecular underpinnings of these diseases, identifying an array of recurrently mutated genes involved in epigenetic regulation, RNA splicing, transcription, and cell signaling. Read More

Blood 2020 10;136(16):1851-1862

Munich Leukemia Laboratory (MLL), Munich, Germany.

More than 90% of patients with myelodysplastic/myeloproliferative neoplasms (MDSs/MPNs) harbor somatic mutations in myeloid-related genes, but still, current diagnostic criteria do not include molecular data. We performed genome-wide sequencing techniques to characterize the mutational landscape of a large and clinically well-characterized cohort including 367 adults with MDS/MPN subtypes, including chronic myelomonocytic leukemia (CMML; n = 119), atypical chronic myeloid leukemia (aCML; n = 71), MDS/MPN with ring sideroblasts and thrombocytosis (MDS/MPN-RS-T; n = 71), and MDS/MPN unclassifiable (MDS/MPN-U; n = 106). A total of 30 genes were recurrently mutated in ≥3% of the cohort. Read More

Best Pract Res Clin Haematol 2020 06 6;33(2):101132. Epub 2019 Dec 6.

Section of Hematology, Department of Internal Medicine, Yale University School of Medicine, New Haven, USA; Yale Cancer Center, New Haven, USA.

The clinicopathology of MDS and MPN are not mutually exclusive and for this reason the category of myelodysplastic syndrome/myeloproliferative neoplasm (MDS/MPN) exists. Several sub-entities have been included under the MDS/MPN umbrella, including MDS/MPN-unclassifiable (MDS/MPN-U) for those cases whose morphologic and clinical phenotype do not meet criteria to be classified as any other MDS/MPN sub-entity. Though potentially regarded as a wastebasket diagnosis, since its integration into myeloid disease classification, MDS/MPN-U has been refined with increasing understanding of the mutational and genomic events that drive particular clinicopathologic phenotypes, even within MDS/MPN-U. Read More

Biol Blood Marrow Transplant 2020 09 23;26(9):1607-1611. Epub 2020 May 23.

Department of Hematopoietic Stem Cell Transplantation, National Cancer Center Hospital, Tokyo, Japan.

To date, there are no data focusing on outcomes of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in patients with myelodysplastic/myeloproliferative neoplasms, unclassifiable (MDS/MPN-U). This study aimed to evaluate outcomes and prognostic factors in patients with MDS/MPN-U after allo-HSCT using Japanese nationwide registry data. The primary endpoint was 3-year overall survival (OS); secondary endpoints included the cumulative incidence of relapse and nonrelapse mortality (NRM). Read More

Leuk Lymphoma 2019 10 7;60(10):2483-2487. Epub 2019 Mar 7.

Division of Hematology, Mayo Clinic , Rochester , MN , USA.

Myelodysplastic syndrome unclassifiable (MDS-U) is a small subtype of myelodysplastic syndromes (MDS). However, rare literature exists in terms of natural progression and clinical outcome of patients with MDS-U. In the present study, we investigated the characteristics and the clinical outcomes of patients categorized as MDS-U based on 2008 World Health Organization criteria (WHO) in a single center comparing to other MDS groups. Read More

Leukemia 2020 02 11;34(2):656-661. Epub 2019 Sep 11.

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

Mayo Clin Proc 2019 08;94(8):1467-1474

Division of Hematology, Mayo Clinic, Rochester, MN.

Objective: To study the changes in overall outcome of patients with myelodysplastic syndromes (MDSs) after approval of several treatments.

Patients And Methods: We identified 54,953 MDS cases in the National Cancer Data Base diagnosed from January 1, 2004, through December 31, 2013, using International Classification of Diseases for Oncology, 3rd edition, codes 9980, 9982-9983, 9985-9987, 9989, 9991-9992. Overall survival and different subgroups were studied over 3 periods of diagnoses (2004-2006, 2007-2009, and 2010-2013). Read More

Blood 2019 09 31;134(11):867-879. Epub 2019 Jul 31.

Division of Hematology and Medical Oncology, and.

Chronic neutrophilic leukemia (CNL), atypical chronic myeloid leukemia (aCML), and myelodysplastic/myeloproliferative neoplasms, unclassifiable (MDS/MPN-U) are a group of rare and heterogeneous myeloid disorders. There is strong morphologic resemblance among these distinct diagnostic entities as well as a lack of specific molecular markers and limited understanding of disease pathogenesis, which has made diagnosis challenging in certain cases. The treatment has remained empirical, resulting in dismal outcomes. Read More

Int J Hematol 2019 Nov 15;110(5):635-639. Epub 2019 Jul 15.

Department of Internal Medicine, Seoul St. Mary's Hematology Hospital, College of Medicine, The Catholic University of Korea, Banpo-daero 222, Seocho-Gu, Seoul, 06591, Republic of Korea.

Graft-versus-host disease (GVHD) is a serious complication of allogeneic stem cell transplantation (SCT). Here, we report a rare case of GVHD involving the central nervous system (CNS). A 35-year-old woman was diagnosed with myelodysplastic syndrome unclassifiable and underwent allogeneic peripheral blood SCT for disease progression to myelodysplastic syndrome with excess blasts-2. Read More

Haematologica 2019 03 4;104(3):497-504. Epub 2018 Oct 4.

Department of Hematology, CHU Grenoble-Alpes, Grenoble.

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