Faculty Profiles - MURAMATSU, Hideki

Integrated diagnosis based on transcriptome analysis in suspected pediatric sarcomas Reviewed

Ichikawa D., Yamashita K., Okuno Y., Muramatsu H., Murakami N., Suzuki K., Kojima D., Kataoka S., Hamada M., Taniguchi R., Nishikawa E., Kawashima N., Narita A., Nishio N., Hama A., Kasai K., Mizuno S., Shimoyama Y., Nakaguro M., Okita H., Kojima S., Nakazawa A., Takahashi Y.

npj Genomic Medicine Vol. 6 ( 1 ) page： 49 2021.12

Language：Japanese Publisher：npj Genomic Medicine

Pediatric solid tumors are a heterogeneous group of neoplasms with over 100 subtypes. Clinical and histopathological diagnosis remains challenging due to the overlapping morphological and immunohistochemical findings and the presence of atypical cases. To evaluate the potential utility of including RNA-sequencing (RNA-seq) in the diagnostic process, we performed RNA-seq in 47 patients with suspected pediatric sarcomas. Histopathologists specialized in pediatric cancer re-evaluated pathological specimens to reach a consensus diagnosis; 42 patients were diagnosed with known subtypes of solid tumors whereas 5 patients were diagnosed with undifferentiated sarcoma. RNA-seq analysis confirmed and refined consensus diagnoses and further identified diagnostic genetic variants in four of the five patients with undifferentiated sarcoma. Genetic lesions were detected in 23 patients, including the novel SMARCA4-THOP1 fusion gene and 22 conventional or recently reported genetic events. Unsupervised clustering analysis of the RNA-seq data identified a distinct cluster defined by the overexpression of rhabdomyosarcoma-associated genes including MYOG and CHRNG. These findings suggest that RNA-seq-based genetic analysis may aid in the diagnosis of suspected pediatric sarcomas, which would be useful for the development of stratified treatment strategies.

DOI： 10.1038/s41525-021-00210-y

Next-Generation Sequencing to Detect Pathogens in Pediatric Febrile Neutropenia: A Single-Center Retrospective Study of 112 Cases Reviewed

A neonate diagnosed with Noonan syndrome with myeloproliferative change Reviewed

Nagatomo K., Fukushima H., Kanai Y., Muramatsu H., Takada H.

Pediatrics International Vol. 63 ( 12 ) page： 1521 - 1523 2021.12

Horiba K., Torii Y., Okumura T., Takeuchi S., Suzuki T., Kawada J.I., Muramatsu H., Takahashi Y., Ogi T., Ito Y.

Open Forum Infectious Diseases Vol. 8 ( 11 ) 2021.11

Publisher：Open Forum Infectious Diseases

Background. Febrile neutropenia (FN) is a frequent complication in immunocompromised patients. However, causative microorganisms are detected in only 10% of patients. This study aimed to detect the microorganisms that cause FN using next-generation sequencing (NGS) to identify the genome derived from pathogenic microorganisms in the bloodstream. Here, we implemented a metagenomic approach to comprehensively analyze microorganisms present in clinical samples from patients with FN. Methods. FN is defined as a neutrophil count <500 cells/µL and fever ≥37.5°C. Plasma/serum samples of 112 pediatric patients with FN and 10 patients with neutropenia without fever (NE) were sequenced by NGS and analyzed by a metagenomic pipeline, PATHDET. Results. The putative pathogens were detected by NGS in 5 of 10 FN patients with positive blood culture results, 15 of 87 FN patients (17%) with negative blood culture results, and 3 of 8 NE patients. Several bacteria that were common in the oral, skin, and gut flora were commonly detected in blood samples, suggesting translocation of the human microbiota to the bloodstream in the setting of neutropenia. The cluster analysis of the microbiota in blood samples using NGS demonstrated that the representative bacteria of each cluster were mostly consistent with the pathogens in each patient. Conclusions. NGS technique has great potential for detecting causative pathogens in patients with FN. Cluster analysis, which extracts characteristic microorganisms from a complex microbial population, may be effective to detect pathogens in minute quantities of microbiota, such as those from the bloodstream.

DOI： 10.1093/ofid/ofab223

Acquisition of a rare NUP98–BPTF fusion gene associated with recurrence of acute myeloid leukemia Reviewed

Kawaguchi K., Azumi S., Itakura Y., Takachi T., Ogura T., Horikoshi Y., Suzuki K., Muramatsu H., Hama A., Takahashi Y., Watanabe K.

Pediatric Blood and Cancer Vol. 68 ( 10 ) page： e29201 2021.10

Clinical diagnostic value of telomere length measurement in inherited bone marrow failure syndromes Reviewed

Miwata S., Narita A., Okuno Y., Suzuki K., Hamada M., Yoshida T., Imaya M., Yamamori A., Wakamatsu M., Narita K., Kitazawa H., Ichikawa D., Taniguchi R., Kawashima N., Nishikawa E., Nishio N., Kojima S., Muramatsu H., Takahashi Y.

Haematologica Vol. 106 ( 9 ) page： 2511 - 2515 2021.9

Echocardiography Monitoring of Pulmonary Hypertension after Pediatric Hematopoietic Stem Cell Transplantation: Pediatric Pulmonary Arterial Hypertension and Pulmonary Veno-Occlusive Disease after Hematopoietic Stem Cell Transplantation Reviewed

Kawashima N., Fukasawa Y., Nishikawa E., Ohta-Ogo K., Ishibashi-Ueda H., Hamada M., Ichikawa D., Narita A., Okuno Y., Muramatsu H., Nishio N., Kojima S., Kato T., Takahashi Y.

Transplantation and Cellular Therapy Vol. 27 ( 9 ) page： 786.e1 - 786.e8 2021.9

Language：Japanese Publisher：Transplantation and Cellular Therapy

Pulmonary hypertension (PH) is associated with high morbidity in children undergoing hematopoietic stem cell transplantation (HSCT). However, owing to the lack of sequential echocardiography, the nature of the condition is not fully understood. This study was conducted to investigate whether routine echocardiography performed after HSCT could detect patients with PH at an earlier stage and elucidate the role of intervention using tadalafil. The study population comprised 93 consecutive children age <18 years who underwent a total of 109 HSCTs. All patients underwent routine transthoracic echocardiography during HSCT. Four children (4%) with a median age of 4 years (range, 0.7 to 6 years) were found to have PH, and their median tricuspid regurgitation peak velocity (TRV) was 4.1 m/s (range, 3.5 to 4.2 m/s). PH was diagnosed at a median of 52 days (range, 21 to 118 days) after HSCT. Three of them were diagnosed with neuroblastoma, and 1 was diagnosed with infantile leukemia. One patient developed PH after autologous HSCT, and 3 received killer immunoglobulin-like receptor ligand-mismatched cord blood. Busulfan was used for conditioning in all patients, and the proportion of patients receiving this medication was significantly higher in the PH group compared with the non-PH group (100% versus 30%; P =.011). Three of the 4 patients had a durable response (TRV ≤2.8 m/s) at a median of 46 days (range, 14 to 79 days) after starting treatment with tadalafil. No patient experienced exacerbation of PH, and treatment was completed at median of 96 days (range, 46 to 212 days). Our data suggest that routine echocardiography monitoring after HSCT should be considered in children receiving busulfan, although the precise follow-up timing needs further study. In addition, safe and effective administration of tadalafil must be ensured by close monitoring.

DOI： 10.1016/j.jtct.2021.05.017

Autoantibodies against the plakin family proteins as a novel marker for chronic graft-versus-host disease of the lung Reviewed

Kawashima N., Nishikawa E., Tsuchisaka A., Hashimoto T., Okuno Y., Hamada M., Ichikawa D., Narita A., Muramatsu H., Nishio N., Kojima S., Muro Y., Takahashi Y.

Bone Marrow Transplantation Vol. 56 ( 9 ) page： 2291 - 2294 2021.9

Relationship between plasma rabbit anti-thymocyte globulin concentration and immunosuppressive therapy response in patients with severe aplastic anemia Reviewed

Narita A., Muramatsu H., Ichikawa D., Hamada M., Nishikawa E., Suzuki K., Kawashima N., Okuno Y., Nishio N., Hama A., Yamazaki H., Nakao S., Kojima S., Takahashi Y.

European Journal of Haematology Vol. 107 ( 2 ) page： 255 - 264 2021.8

Language：Japanese Publisher：European Journal of Haematology

Objectives: Patients with acquired aplastic anemia (AA) without HLA-matched sibling donors or aged >40 years receive immunosuppressive therapy (IST) with anti-thymocyte globulin (ATG). We investigated the relationship between plasma rabbit ATG (r-ATG) concentration and IST response. Methods: From May 2012 to October 2017, 81 patients with severe AA who required initial IST were included. A 1:1 block randomization was employed for 2.5 and 3.5 mg/kg doses of r-ATG. Results: No significant difference in response rates was observed between the 2.5 and 3.5 mg/kg groups (63% vs. 58%, P =.894). Median r-ATG concentrations on days 14 and 28 after IST were 15.2 (0.0-97.7) and 1.8 (0.0-74.9 µg/mL), respectively. According to r-ATG concentration, response rates were significantly higher in the group with higher r-ATG concentration than in those with lower r-ATG concentration (day 14, 88% vs. 52%; P =.006 and day 28, 79% vs. 46%; P =.005). In multivariate analysis, higher r-ATG concentrations at day 28 were independent predictors of favorable response to IST at 6 months (odds ratio, 0.29; 95% confidence interval, 0.09-0.93; P =.037). Conclusions: The present data indicate that higher r-ATG concentration at day 28 resulted in improved IST response.

DOI： 10.1111/ejh.13644

Successful treatment of a novel type I interferonopathy due to a de novo PSMB9 gene mutation with a Janus kinase inhibitor Reviewed

Kataoka S., Kawashima N., Okuno Y., Muramatsu H., Miwata S., Narita K., Hamada M., Murakami N., Taniguchi R., Ichikawa D., Kitazawa H., Suzuki K., Nishikawa E., Narita A., Nishio N., Yamamoto H., Fukasawa Y., Kato T., Yamamoto H., Natsume J., Kojima S., Nishino I., Taketani T., Ohnishi H., Takahashi Y.

Journal of Allergy and Clinical Immunology Vol. 148 ( 2 ) page： 639 - 644 2021.8

Language：Japanese Publisher：Journal of Allergy and Clinical Immunology

Background: Type I interferonopathies are a recently established subgroup of autoinflammatory diseases caused by mutations in genes associated with proteasome degradation or cytoplasmic RNA- and DNA-sensing pathways. Objective: This study aimed to unveil the molecular pathogenesis of a patient with novel type I interferonopathy, for which no known genetic mutations have been identified. Methods: We performed the whole-exome sequencing of a 1-month-old boy with novel type I interferonopathy. We also investigated proteasome activities using patient-derived B lymphoblastoid cell lines (LCLs) and normal LCLs transduced with the mutant gene. Results: Whole-exome sequencing identified a de novo proteasome 20S subunit beta 9 (PSMB9) p.G156D mutation in the patient who developed fever, a chilblain-like skin rash, myositis, and severe pulmonary hypertension due to the hyperactivation of IFN-α. Patient-derived LCLs revealed reduced proteasome activities, and exogenous transduction of mutant PSMB9 p.G156D into normal LCLs significantly suppressed proteasome activities, and the endogenous PSMB9 protein was lost along with the reduction of other immunoproteasome subunits, PSMB8 and PSMB10 proteins. He responded to the administration of a Janus kinase inhibitor, tofacitinib, and he was successfully withdrawn from venoarterial extracorporeal membranous oxygenation. At age 7 months, he received an unrelated cord blood transplantation. At 2 years posttransplantation, he no longer required tofacitinib and experienced no disease recurrence. Conclusions: We present the case of a patient with a novel type I interferonopathy caused by a de novo PSMB9 p.G156D mutation that suppressed the wild-type PSMB9 protein expression. Janus kinase inhibitor and stem cell transplantation could be curative therapies in patients with severe interferonopathies.

DOI： 10.1016/j.jaci.2021.03.010

Correction: Reduced-intensity conditioning is effective for hematopoietic stem cell transplantation in young pediatric patients with Diamond-Blackfan anemia (Bone Marrow Transplantation, (2021), 56, 5, (1013-1020), 10.1038/s41409-020-01056-1) Reviewed

Koyamaishi S., Kamio T., Kobayashi A., Sato T., Kudo K., Sasaki S., Kanezaki R., Hasegawa D., Muramatsu H., Takahashi Y., Sasahara Y., Hiramatsu H., Kakuda H., Tanaka M., Ishimura M., Nishi M., Ishiguro A., Yabe H., Sarashina T., Yamamoto M., Yuza Y., Hyakuna N., Yoshida K., Kanno H., Ohga S., Ohara A., Kojima S., Miyano S., Ogawa S., Toki T., Terui K., Ito E.

Bone Marrow Transplantation Vol. 56 ( 5 ) page： 1218 - 1219 2021.5

Reduced-intensity conditioning is effective for hematopoietic stem cell transplantation in young pediatric patients with Diamond–Blackfan anemia Reviewed

Bone Marrow Transplantation Vol. 56 ( 5 ) page： 1013 - 1020 2021.5

Language：Japanese Publisher：Bone Marrow Transplantation

Allogeneic hematopoietic stem cell transplantation (HSCT) is the only curative therapy for the hematologic manifestations of Diamond–Blackfan anemia (DBA). However, data regarding the optimal conditioning regimen for DBA patients are limited. We retrospectively compared the outcomes of DBA patients who underwent HSCT using either myeloablative conditioning (MAC) or reduced-intensity conditioning (RIC) regimens. The patients belonged to a cohort treated at our hospitals between 2000 and 2018. HSCT was performed in 27 of 165 patients (16.4%). The median age at the time of HSCT was 3.6 years. Stem cell sources included bone marrow for 25 patients (HLA-matched sibling donors, n = 5; HLA-mismatched related donors, n = 2; HLA-matched/mismatched unrelated donors, n = 18) or cord blood for 2 patients. MAC or RIC regimens were used in 12 and 15 patients, respectively. Engraftment was successful in all 27 patients who underwent HSCT. Three patients who underwent HSCT using MAC regimens developed sinusoidal obstruction syndrome. The 3-year overall survival (OS) and failure-free survival rates (FFS) post-transplantations were 95.2% and 88.4%, respectively, with no significant differences between MAC and RIC regimens. Our data suggest that HSCTs using RIC regimens are effective and obtain engraftment with excellent OS and FFS for young DBA patients.

DOI： 10.1038/s41409-020-01056-1

Predictive factors for the development of leukemia in patients with transient abnormal myelopoiesis and Down syndrome Reviewed

Yamato G., Deguchi T., Terui K., Toki T., Watanabe T., Imaizumi T., Hama A., Iwamoto S., Hasegawa D., Ueda T., Yokosuka T., Tanaka S., Yanagisawa R., Koh K., Saito A.M., Horibe K., Hayashi Y., Adachi S., Mizutani S., Taga T., Ito E., Watanabe K., Muramatsu H.

Leukemia Vol. 35 ( 5 ) page： 1480 - 1484 2021.5

The eldest case of MICPCH with CASK mutation exhibiting gross motor regression Reviewed

Nishio Y., Kidokoro H., Takeo T., Narita H., Sawamura F., Narita K., Kawano Y., Nakata T., Muramatsu H., Hara S., Kaname T., Natsume J.

Brain and Development Vol. 43 ( 3 ) page： 459 - 463 2021.3

Language：Japanese Publisher：Brain and Development

Background: MICPCH is manifested as microcephaly associated with pontocerebellar hypoplasia and global developmental delay but developmental regression has never been reported. We describe the detailed clinical history of a woman with intellectual disability and microcephaly with pontine and cerebellar hypoplasia (MICPCH) with a CASK mutation who exhibited gross motor regression after adolescence. Case: The patient experienced severe motor and intellectual developmental delay with microcephaly from infancy. The initial diagnosis was Rett syndrome based on her clinical features, including hand stereotypes and the absence of structural abnormality on magnetic resonance imaging (MRI) performed at the age of 5 years. Although gross motor abilities developed slowly and she could walk independently, she never acquired speech or understanding of languages. After adolescence, her motor ability gradually regressed so that she was unable to stand without support and moved with a wheelchair. At the age of 31 years, because of her atypical clinical course for Rett syndrome, whole exome sequencing was performed, which revealed a de novo heterozygous c.2068 + 1G > A mutation in the CASK gene (NM_001126055). Brain MRI revealed mild pontocerebellar hypoplasia compatible with the clinical phenotype of MICPCH. Discussion: This case suggests that MICPCH with a CASK mutation might cause developmental regression after adolescence and might be regarded as a neurodegenerative disorder.

DOI： 10.1016/j.braindev.2020.11.007

International consensus definition of DNA methylation subgroups in juvenile myelomonocytic leukemia Reviewed

Schonung M., Meyer J., Nollke P., Olshen A.B., Hartmann M., Murakami N., Wakamatsu M., Okuno Y., Plass C., Loh M.L., Niemeyer C.M., Muramatsu H., Flotho C., Stieglitz E., Lipka D.B.

Clinical Cancer Research Vol. 27 ( 1 ) page： 158 - 168 2021.1

Language：Japanese Publisher：Clinical Cancer Research

Purpose: Known clinical and genetic markers have limitations in predicting disease course and outcome in juvenile myelomonocytic leukemia (JMML). DNA methylation patterns in JMML have correlated with outcome across multiple studies, suggesting it as a biomarker to improve patient stratification. However, standardized approaches to classify JMML on the basis of DNA methylation patterns are lacking. We, therefore, sought to define an international consensus for DNA methylation subgroups in JMML and develop classification methods for clinical implementation. Experimental Design: Published DNA methylation data from 255 patients with JMML were used to develop and internally validate a classifier model. Accuracy across platforms (EPIC-arrays and MethylSeq) was tested using a technical validation cohort (32 patients). The suitability of both methods for single-patient classification was demonstrated using an independent cohort (47 patients). Results: Analysis of pooled, published data established three DNA methylation subgroups as a de facto standard. Unfavorable prognostic parameters (PTPN11 mutation, elevated fetal hemoglobin, and older age) were significantly enriched in the high methylation (HM) subgroup. A classifier was then developed that predicted subgroups with 98% accuracy across different technological platforms. Applying the classifier to an independent validation cohort confirmed an association of HM with secondary mutations, high relapse incidence, and inferior overall survival (OS), while the low methylation subgroup was associated with a favorable disease course. Multivariable analysis established DNA methylation subgroups as the only significant factor predicting OS. Conclusions: This study provides an international consensus definition for DNA methylation subgroups in JMML. We developed and validated methods which will facilitate the design of risk-stratified clinical trials in JMML.

DOI： 10.1158/1078-0432.CCR-20-3184

Detection of subclonal SETBP1 and JAK3 mutations in juvenile myelomonocytic leukemia using droplet digital PCR Reviewed

Wakamatsu M., Okuno Y., Murakami N., Miwata S., Kitazawa H., Narita K., Kataoka S., Ichikawa D., Hamada M., Taniguchi R., Suzuki K., Kawashima N., Nishikawa E., Narita A., Nishio N., Kojima S., Muramatsu H., Takahashi Y.

Leukemia Vol. 35 ( 1 ) page： 259 - 263 2021.1

Usefulness of functional splicing analysis to confirm precise disease pathogenesis in Diamond-Blackfan anemia caused by intronic variants in RPS19 Reviewed

Takafuji S., Mori T., Nishimura N., Yamamoto N., Uemura S., Nozu K., Terui K., Toki T., Ito E., Muramatsu H., Takahashi Y., Matsuo M., Yamamura T., Iijima K.

Pediatric Hematology and Oncology Vol. 38 ( 6 ) page： 515 - 527 2021

Language：Japanese Publisher：Pediatric Hematology and Oncology

Diamond-Blackfan anemia (DBA) is mainly caused by pathogenic variants in ribosomal proteins and 22 responsible genes have been identified to date. The most common causative gene of DBA is RPS19 [NM_001022.4]. Nearly 180 RPS19 variants have been reported, including three deep intronic variants outside the splicing consensus sequence (c.72-92A > G, c.356 + 18G > C, and c.411 + 6G > C). We also identified one case with a c.412-3C > G intronic variant. Without conducting transcript analysis, the pathogenicity of these variants is unknown. However, it is difficult to assess transcripts because of their fragility. In such cases, in vitro functional splicing assays can be used to assess pathogenicity. Here, we report functional splicing analysis results of four RPS19 deep intronic variants identified in our case and in previously reported cases. One splicing consensus variant (c.411 + 1G > A) was also examined as a positive control. Aberrant splicing with a 2-bp insertion between exons 5 and 6 was identified in the patient samples and minigene assay results also identified exon 6 skipping in our case. The exon 6 skipping transcript was confirmed by further evaluation using quantitative RT-PCR. Additionally, minigene assay analysis of three reported deep intronic variants revealed that none of them showed aberrant splicing and that these variants were not considered to be pathogenic. In conclusion, the minigene assay is a useful method for functional splicing analysis of inherited disease.

DOI： 10.1080/08880018.2021.1887984

Two Aldehyde Clearance Systems Are Essential to Prevent Lethal Formaldehyde Accumulation in Mice and Humans Reviewed

Dingler F.A., Wang M., Mu A., Millington C.L., Oberbeck N., Watcham S., Pontel L.B., Kamimae-Lanning A.N., Langevin F., Nadler C., Cordell R.L., Monks P.S., Yu R., Wilson N.K., Hira A., Yoshida K., Mori M., Okamoto Y., Okuno Y., Muramatsu H., Shiraishi Y., Kobayashi M., Moriguchi T., Osumi T., Kato M., Miyano S., Ito E., Kojima S., Yabe H., Yabe M., Matsuo K., Ogawa S., Göttgens B., Hodskinson M.R.G., Takata M., Patel K.J.

Molecular Cell Vol. 80 ( 6 ) page： 996 - 1012.e9 2020.12

Language：Japanese Publisher：Molecular Cell

Dingler et al. show that formaldehyde is produced endogenously at sufficient levels to induce and overwhelm DNA repair. Two enzymes, ADH5 and ALDH2, are critical in clearance of formaldehyde, whose loss results in a bone marrow failure and leukemia syndrome of purely metabolic origin.

DOI： 10.1016/j.molcel.2020.10.012

Digenic mutations in ALDH2 and ADH5 impair formaldehyde clearance and cause a multisystem disorder, AMeD syndrome Reviewed

Oka Y., Hamada M., Nakazawa Y., Muramatsu H., Okuno Y., Higasa K., Shimada M., Takeshima H., Hanada K., Hirano T., Kawakita T., Sakaguchi H., Ichimura T., Ozono S., Yuge K., Watanabe Y., Kotani Y., Yamane M., Kasugai Y., Tanaka M., Suganami T., Nakada S., Mitsutake N., Hara Y., Kato K., Mizuno S., Miyake N., Kawai Y., Tokunaga K., Nagasaki M., Kito S., Isoyama K., Onodera M., Kaneko H., Matsumoto N., Matsuda F., Matsuo K., Takahashi Y., Mashimo T., Kojima S., Ogi T.

Science Advances Vol. 6 ( 51 ) 2020.12

Language：Japanese Publisher：Science Advances

Rs671 in the aldehyde dehydrogenase 2 gene (ALDH2) is the cause of Asian alcohol flushing response after drinking. ALDH2 detoxifies endogenous aldehydes, which are the major source of DNA damage repaired by the Fanconi anemia pathway. Here, we show that the rs671 defective allele in combination with mutations in the alcohol dehydrogenase 5 gene, which encodes formaldehyde dehydrogenase (ADH5FDH), causes a previously unidentified disorder, AMeD (aplastic anemia, mental retardation, and dwarfism) syndrome. Cellular studies revealed that a decrease in the formaldehyde tolerance underlies a loss of differentiation and proliferation capacity of hematopoietic stem cells. Moreover, Adh5−/−Aldh2E506K/E506K double-deficient mice recapitulated key clinical features of AMeDS, showing short life span, dwarfism, and hematopoietic failure. Collectively, our results suggest that the combined deficiency of formaldehyde clearance mechanisms leads to the complex clinical features due to overload of formaldehyde-induced DNA damage, thereby saturation of DNA repair processes.

DOI： 10.1126/SCIADV.ABD7197

Myelodysplastic syndromes in a pediatric patient with Cri du Chat syndrome with a ring chromosome 5 Reviewed

Nozawa A., Ozeki M., Yasue S., Endo S., Kadowaki T., Ohnishi H., Muramatsu H., Hama A., Takahashi Y., Kojima S., Fukao T.

International Journal of Hematology Vol. 112 ( 5 ) page： 728 - 733 2020.11

Language：Japanese Publisher：International Journal of Hematology

Few hematological complications have previously been reported in association with Cri du Chat syndrome (CdCS). A case of myelodysplastic syndromes (MDS) in a pediatric patient with CdCS is herein presented. A 17-year-old female with CdCS caused by ring chromosome 5 was admitted to the hospital for investigation of a 1-month history of anemia. Based on the morphological findings of bone marrow, the patient was diagnosed with refractory cytopenia with multilineage dysplasia. The risk group was classified as intermediate-1 in the International Prognostic Scoring System (IPSS), and low in the revised IPSS. Assessment by microarray comparative genomic hybridization (CGH) identified the breakpoints of ring chromosome 5 as 46,XX,r(5)(p14.3q35.3). This revealed that the 5q terminal deletion did not include the common deleted region of MDS with del(5q). Treatment with azacitidine was initiated to control disease progression and improve quality of life. At baseline, the patient had a mean transfusion requirement of 3 units/month, which decreased to 2 units/month after six cycles of azacitidine and to 1 unit/month after 10 cycles of azacitidine. Cytopenia observed in the presented case seemed irrelevant to ring chromosome 5 which is the causative cytogenetic abnormality of CdCS, and further analyses may be needed to clarify the pathogenesis.

DOI： 10.1007/s12185-020-02909-7