Telomere integrated scoring system of myelodysplastic syndrome.

Introduction: Recently, multigene target sequencing is widely performed for the purpose of prognostic prediction and application of targeted therapy. Here, we proposed a new scoring system that encompasses gene variations, telomere length, and Revised International Prognostic Scoring System (IPSS-R) together in Asian myelodysplastic syndrome.

Methods: We developed a new scoring model of these variables: age ≥ 65 years + IPSS-R score + ASXL1 mutation + TP53 mutation + Telomere length (<5.

Ultradeep Sequencing Analysis of Paroxysmal Nocturnal Hemoglobinuria Clones Detected by Flow Cytometry: PIG Mutation in Small PNH Clones.

Objectives: We aimed to determine whether small paroxysmal nocturnal hemoglobinuria (PNH) clones detected by flow cytometry (FCM) harbor PIG gene mutations with quantitative correlation.

Methods: We analyzed 89 specimens from 63 patients whose PNH clone size was ≥0.1% by FCM.

Mutation of ten-eleven translocation-2 is associated with increased risk of autoimmune disease in patients with myelodysplastic syndrome.

Background/aims: Myelodysplastic syndrome (MDS) is caused by genetic and epigenetic alteration of hematopoietic precursors and immune dysregulation. Approximately 20% of patients with MDS develop an autoimmune disease (AID). Here, we investigated whether particular genetic mutations are associated with AID in patients with MDS.

The Implication of Cytogenetic Alterations in Pancreatic Ductal Adenocarcinoma and Intraductal Papillary Mucinous Neoplasm Identified by Fluorescence Hybridization and Their Potential Diagnostic Utility.

Background/aims: We investigated chromosomal aberrations in patients with pancreatic ductal adenocarcinoma (PDAC) and intraductal papillary mucinous neoplasm (IPMN) by fluorescence hybridization (FISH) to identify cytogenetic changes and molecular markers that may be useful for preoperative diagnosis.

Methods: Tissue samples from 48 PDAC and 17 IPMN patients were investigated by FISH analysis using probes targeting chromosomes 7q, 17p, 18q, 20q, and 21q and the pericentromeric region of chromosome 18 (CEP18).

Results: The PDAC samples harbored 17p deletion (95.

Telomere length and its correlation with gene mutations in chronic lymphocytic leukemia in a Korean population.

Telomere length (TL) is a prognostic indicator in Caucasian chronic lymphocytic leukemia (CLL), but its significance in Asian CLL remains unknown. To investigate the prognostic significance of TL and its correlation with cytogenetic aberrations and somatic mutations, we analyzed TL measurements at the cellular level by interphase fluorescence in situ hybridization in patients with CLL in Korea. The present study enrolled 110 patients (41 females and 69 males) diagnosed with CLL according to the World Health Organization criteria (2001-2017).

Characteristics of Waldenström Macroglobulinemia in Korean Patients According to Mutational Status of MYD88 and CXCR4: Analysis Using Ultra-Deep Sequencing.

Background: Little is known about the mutational frequency of myeloid differentiation factor 88 (MYD88) and C-X-C chemokine receptor type 4 (CXCR4) and the corresponding characteristics in Asian individuals afflicted with Waldenström macroglobulinemia (WM). We investigated the characteristics of WM according to mutational status of MYD88/CXCR4, and attempted to determine the lineage commitment among hematopoietic cells by MYD88 single-cell sequencing on bone marrow (BM) smear slides.

Materials And Methods: CXCR4 mutations (muts) were detected using ultra-deep sequencing using target capture.

Replicative senescence of hematopoietic cells in patients with idiopathic cytopenia of undetermined significance.

We hypothesized that a subset of idiopathic cytopenia of undetermined significance (ICUS) is associated with an increased autonomous proliferation with exhaustion of hematopoiesis. The aim of this study was to investigate the cell turnover rate and replicative history of the bone marrow cells of ICUS patients. To this end, we examined telomere length (TL), proliferation, and apoptosis of the bone marrow cells of ICUS patients and healthy controls (HCs) using telomere quantitative fluorescence in situ hybridization and immunohistochemical staining for Ki-67 and cleaved caspase-3.

Monozygotic twins with shared de novo GATA2 mutation but dissimilar phenotypes due to differential promoter methylation.

A revised WHO classification of hematopoietic neoplasm introduced the new category 'Myeloid Neoplasms with Germline Predisposition', reflecting the growing importance of genetic testing for myeloid neoplasms. Here, we investigated monozygotic twins with the same de novo mutation in GATA2 but different phenotypes. The patient suffering a bleeding tendency was diagnosed with myelodysplastic syndrome (MDS), and her monozygotic twin showed dysmegakaryopoietic features in the bone marrow.

ASXL1 is a molecular predictor in idiopathic cytopenia of undetermined significance.

We analyzed the mutational profile of idiopathic cytopenia of undetermined significance (ICUS) compared with that of myelodysplastic syndrome (MDS). Targeted sequencing of 88 genes associated with myeloid malignancies was performed using samples of bone marrow mononuclear cells from ICUS and MDS patients. Forty patients with ICUS and 128 patients with MDS were included in this study.

Shifting of erythroleukemia to myelodysplastic syndrome according to the revised WHO classification: Biologic and cytogenetic features of shifted erythroleukemia.

The 2016 revision of the World Health Organization (WHO) classification of tumours of haematopoietic and lymphoid tissues was published. According to 2016 WHO criteria, diagnostic criteria of acute erythroid leukemia was revised. We reassessed 34 de novo acute erythroid leukemia (AEL) diagnosed by 2008 WHO criteria, according to 2016 WHO criteria.

Idiopathic hypereosinophilia is clonal disorder? Clonality identified by targeted sequencing.

Idiopathic hypereosinophilia (IHE)/idiopathic hypereosinophilic syndrome (IHES) has been defined by a persistent elevation of the blood eosinophil count exceeding 1.5×103/μL, without evidence of reactive or clonal causes. While T-cell clonality assessment has been recommended for unexplained hypereosinophilia, this approach is not often applied to routine practice in the clinic.

The high frequency of the U2AF1 S34Y mutation and its association with isolated trisomy 8 in myelodysplastic syndrome in Asians, but not in Caucasians.

Mutational profiles of 153 Korean myelodysplastic syndrome (MDS) patients were investigated. Sequencing of 87 genes presented similar mutational profiles in Korean MDS patients compared with previous reports. The most frequently mutated genes were ASXL1 (22.

Telomere length and somatic mutations in correlation with response to immunosuppressive treatment in aplastic anaemia.

We investigated the frequencies of cytogenetic aberrations and somatic mutations of prognostic relevance in 393 patients with aplastic anaemia (AA). Clonality was determined by G-banding/fluorescence in situ hybridization (FISH) (n = 245), and targeted capture sequencing was performed for 88 haematopoiesis-related genes (n = 70). The telomere length (TL) of bone marrow nucleated cells was measured at the single cell level by FISH (n = 135).

Dysregulation of Telomere Lengths and Telomerase Activity in Myelodysplastic Syndrome.

Background: Telomere shortening is thought to be involved in the pathophysiology of myeloid malignancies, but telomere lengths (TL) during interphase and metaphase in hematopoietic malignancies have not been analyzed. We aimed to assess the TLs of interphase and metaphase cells of MDS and telomerase activity (TA) and to find out prognostic significances of TL and TA.

Methods: The prognostic significance of TA by quantitative PCR and TL by quantitative fluorescence in situ hybridization (QFISH) of interphase nuclei and metaphase chromosome arms of bone marrow cells from patients with MDS were evaluated.

Genomic Profile of Chronic Lymphocytic Leukemia in Korea Identified by Targeted Sequencing.

Chronic lymphocytic leukemia (CLL) is extremely rare in Asian countries and there has been one report on genetic changes for 5 genes (TP53, SF3B1, NOTCH1, MYD88, and BIRC3) by Sanger sequencing in Chinese CLL. Yet studies of CLL in Asian countries using Next generation sequencing have not been reported. We aimed to characterize the genomic profiles of Korean CLL and to find out ethnic differences in somatic mutations with prognostic implications.

Antitumor Effect of KX-01 through Inhibiting Src Family Kinases and Mitosis.

Purpose: KX-01 is a novel dual inhibitor of Src and tubulin. Unlike previous Src inhibitors that failed to show clinical benefit during treatment of breast cancer, KX-01 can potentially overcome the therapeutic limitations of current Src inhibitors through inhibition of both Src and tubulin. The present study further evaluates the activity and mechanism of KX-01 and .

Short telomere length and its correlation with gene mutations in myelodysplastic syndrome.

Background: Telomere erosion can lead to genomic instability and cancer progression. It has been suggested that the shortest telomere, not the average telomere length (TL), is critical for cell viability. Some studies have shown shorter TL in myelodysplastic syndrome (MDS) patients but the critically short telomeres, the variability of TL within individual patient has not been evaluated.

Burden of cytogenetically abnormal plasma cells in light chain amyloidosis and their prognostic relevance.

We performed cytoplasmic fluorescence in situ hybridization assays of light chain amyloidosis (AL). In total, 234 patients were enrolled: 28 patients with AL, 24 with monoclonal gammopathy of undetermined significance (MGUS), and 182 with multiple myeloma (MM). Chromosomal abnormalities were detected in 13 of 22 (59%) AL patients without MM.

CALR, JAK2, and MPL mutation profiles in patients with four different subtypes of myeloproliferative neoplasms: primary myelofibrosis, essential thrombocythemia, polycythemia vera, and myeloproliferative neoplasm, unclassifiable.

Objectives: We investigated mutation profiles of CALR, JAK2, and MPL in 199 Korean patients with myeloproliferative neoplasms (MPNs).

Methods: In total, 199 patients with MPN (54 primary myelofibrosis [PMF], 79 essential thrombocythemia [ET], 58 polycythemia vera [PV], and eight MPN-unclassifiable [MPN-U]) and 4 patients with acute panmyelosis with myelofibrosis (APMF) were retrospectively subjected to Sanger sequencing for CALR, JAK2, and MPL.

Results: The overall frequency of CALR mutations was 12.

A challenging diagnosis: crystal-storing histiocytosis in plasma cell myeloma.

Objectives: Crystal-storing histiocytosis (CSH) is an uncommon finding in plasma cell neoplasms. CSH is thought to be an intralysosomal deposition of secreted paraproteins or immunoglobulins, which usually express κ immunoglobulin light chains that finally aggregate in crystals. Because of its rarity, CSH in bone marrow often makes diagnosis difficult.