Sugar and arginine facilitate oral tolerance by ensuring the functionality of tolerogenic immune cell subsets in the intestine.

Although oral tolerance is a critical system in regulating allergic disorders, the mechanisms by which dietary factors regulate the induction and maintenance of oral tolerance remain unclear. To address this, we explored the differentiation and function of various immune cells in the intestinal immune system under fasting and ad libitum-fed conditions before oral ovalbumin (OVA) administration. Fasting mitigated OVA-specific Treg expansion, which is essential for oral tolerance induction. This abnormality mainly resulted from functional defects in the CX3CR1+ cells responsible for the uptake of luminal OVA and reduction of tolerogenic CD103+ dendritic cells. Eventually, fasting impaired the preventive effect of oral OVA administration on asthma and allergic rhinitis development. Specific food ingredients, namely carbohydrates and arginine, were indispensable for oral tolerance induction by activating glycolysis and mTOR signaling. Overall, prior food intake and nutritional signals are critical for maintaining immune homeostasis by inducing tolerance to ingested food antigens.

Exploring the use of telepractice Dohsa-hou to adults with intellectual disabilities.

This study presents the application of an authentic Japanese bodywork approach Dohsa-hou to adults with intellectual disabilities who live in a care facility. Amid the COVID-19 pandemic, such people remained disconnected from their families and friends, for which reason many of them experience anxiety, stress and inability to enjoy leisure activities. Given the lockdown circumstances, we decided to use for the first time in the field telepractice to provide Dohsa-hou. The results showed that participants experienced a gradual positive mood change and also expressed a desire to continue the sessions. Considering this, although further research is still needed, we assume that telepractice Dohsa-hou might be a viable substitute for the face-to-face sessions.

Metabolic Effects of Short-Term High-Fat Intake Vary Depending on Dietary Amino Acid Composition.

Background: It is generally accepted that excessive fat intake has undesirable effects on the energy metabolism of our body. Dietary amino acid composition is also critical to the regulation of lipid metabolism. Objectives: This study aimed to investigate whether high-fat diets (HFDs) with different amino acid deficiencies lead to different metabolic outcomes. Methods: Six-wk-old male Wistar rats were fed either a control diet (CN; 3.7 kcal/g, 12% calories from fat) or HFDs (5.1 kcal/g, 60% calories from fat) with 7 different amino acid compositions [control or methionine, arginine, histidine, lysine, threonine, or branched-chain amino acids (BCAAs) deficient], for 7 d. Tissue weights and lipid accumulation in the liver, skeletal muscle, and adipose tissue were measured, and serum biochemical parameters were analyzed. Results: Although the food intake of the HFD groups was a little less than that of the CN group, the total calorie intakes were comparable among the groups, except for histidine-deficient and BCAA-deficient groups. In rats fed am HFD with a control amino acid composition (HFCN), dramatic increase in triglyceride (TG) accumulation in the liver and serum LDL cholesterol concentration were observed compared with the CN group. However, when the arginine content in the diet was reduced, liver TG accumulation was completely inhibited, with no apparent effects on serum lipoprotein-cholesterol concentrations. Meanwhile, deficiency of the other amino acids, such as threonine, reversed HFD-induced upregulation of serum LDL cholesterol. Conclusions: It is observed that although the rats ingested an excessive amount of fat, neither ectopic fat accumulation nor dyslipidemia were always induced at least in the short term; hence, the consequent metabolic change was dependent on the dietary amino acid composition. These findings introduce an important perspective regarding HFD regimens in both scientific and clinical contexts.

Identification of triciribine as a novel myeloid cell differentiation inducer.

Differentiation therapy using all-trans retinoic acid (ATRA) for acute promyelocytic leukemia (APL) is well established. However, because the narrow application and tolerance development of ATRA need to be improved, we searched for another efficient myeloid differentiation inducer. Kinase activation is involved in leukemia biology and differentiation block. To identify novel myeloid differentiation inducers, we used a Kinase Inhibitor Screening Library. Using a nitroblue tetrazolium dye reduction assay and real-time quantitative PCR using NB4 APL cells, we revealed that, PD169316, SB203580, SB202190 (p38 MAPK inhibitor), and triciribine (TCN) (Akt inhibitor) potently increased the expression of CD11b. We focused on TCN because it was reported to be well tolerated by patients with advanced hematological malignancies. Nuclear/cytoplasmic (N/C) ratio was significantly decreased, and myelomonocytic markers (CD11b and CD11c) were potently induced by TCN in both NB4 and acute myeloid leukemia (AML) M2 derived HL-60 cells. Western blot analysis using NB4 cells demonstrated that TCN promoted ERK1/2 phosphorylation, whereas p38 MAPK phosphorylation was not affected, suggesting that activation of the ERK pathway is involved in TCN-induced differentiation. We further examined that whether ATRA may affect phosphorylation of ERK and p38, and found that there was no obvious effect, suggesting that ATRA induced differentiation is different from TCN effect. To reveal the molecular mechanisms involved in TCN-induced differentiation, we performed microarray analysis. Pathway analysis using DAVID software indicated that "hematopoietic cell lineage" and "cytokine-cytokine receptor interaction" pathways were enriched with high significance. Real-time PCR analysis demonstrated that components of these pathways including IL1ß, CD3D, IL5RA, ITGA6, CD44, ITGA2B, CD37, CD9, CSF2RA, and IL3RA, were upregulated by TCN-induced differentiation. Collectively, we identified TCN as a novel myeloid cell differentiation inducer, and trials of TCN for APL and non-APL leukemia are worthy of exploration in the future.

Intrahepatic cholangiocarcinoma with arterial phase hyperenhancement and specialized tumor microenvironment associated with good prognosis after radical resection: A single-center retrospective study.

BACKGROUND: This single-center retrospective study aimed to clarify the clinical and pathologic background of mass-forming intrahepatic cholangiocarcinomas. METHODS: A total of 53 patients with mass-forming intrahepatic cholangiocarcinomas were selected from 2007 to 2021 and analyzed based on several parameters, including the preoperative computed tomography pattern (enhancement in the arterial phase of dynamic contrast-enhanced computed tomography), clinical data, and tumor microenvironment evaluated by immunohistochemistry. The hyperenhancement (n = 13) and hypoenhancement (n = 40) groups were defined using the 50% cutoff of tumors with higher attenuation than the liver parenchyma. RESULTS: The hyperenhancement group was characterized by a better overall survival than the hypoenhancement group (5-year survival: 86% vs 27%, respectively; P < .001) and by a higher infiltration of peritumoral (92% vs 58%; P = .020) and intratumoral CD3-positive T lymphocytes (85% vs 35%; P = .002). Conversely, the hypoenhancement group was characterized by a higher infiltration versus peritumoral CD163-positive tumor-associated macrophages (60% vs 8%; P = .001), peritumoral pentraxin 3-positive tumor-associated macrophages (50% vs 15%; P = .024), and intratumoral α-smooth muscle actin-positive cancer-associated fibroblasts (15% vs 68%; P = .001). A multiple regression analysis was performed to predict overall survival from the microenvironment, and the independent poor predictor factors were low intratumoral CD3-positive T lymphocytes (hazard ratio = 2.75), high peritumoral (hazard ratio = 2.38), and intratumoral CD163-positive tumor-associated macrophages (hazard ratio = 2.81) (all P values < 0.05). CONCLUSION: Compared with hypovascular, hypervascular mass-forming intrahepatic cholangiocarcinomas have better tumor immunity and prognosis.

Fucosylation inhibitor 6-alkynylfucose enhances the ATRA-induced differentiation effect on acute promyelocytic leukemia cells.

For acute promyelocytic leukemia (APL), differentiation therapy with all-trans retinoic acid (ATRA) is well established. However, the narrow application and tolerance development of ATRA remain to be improved. In this study, we investigated the effects of combinations of glycosylation inhibitors with ATRA to achieve better efficiency than ATRA alone. We found that the combination of fucosylation inhibitor 6-alkynylfucose (6AF) and ATRA had an additional effect on cell differentiation, as revealed by expression changes in two differentiation markers, CD11b and CD11c, and significant morphological changes in NB4 APL and HL-60 acute myeloid leukemia (AML) cells. In AAL lectin blot analyses, ATRA or 6AF alone could decrease fucosylation, while their combination decreased fucosylation more efficiently. To clarify the molecular mechanism for the 6AF effect on ATRA-induced differentiation, we performed microarray analyses using NB4 cells. In a pathway analysis using DAVID software, we found that the C-type lectin receptor (CLR) signaling pathway was enriched with high significance. In real-time PCR analyses using NB4 and HL-60 cells, FcεRIγ, CLEC6A, CLEC7A, CASP1, IL-1ß, and EGR3, as components of the CLR pathway, as well as CD45 and AKT3 were upregulated by 6AF in ATRA-induced differentiation. Taken together, the present findings suggest that the CLR signaling pathway is involved in the 6AF effect on ATRA-induced differentiation.

Growth hormone resistance induced by amino acid deprivation in fao cells is independent of FGF21.

Adequate dietary intake of amino acids is imperative for normal animal growth. Our previous work using rat hepatocarcinoma Fao cells demonstrated that growth hormone (GH) resistance, coupled with a concurrent reduction in insulin-like growth factor 1 (Igf1) mRNA levels, may underlie the growth retardation associated with a low-protein diet (LPD). In this study, we investigated whether FGF21 contributes to liver GH resistance in Fao rat hepatoma cells under amino acid deprivation conditions. Mice subjected to an LPD exhibited growth retardation, compromised GH signaling in the liver, and decreased blood IGF-1 levels compared with those on a control diet. To assess the potential involvement of fibroblast growth factor (FGF) 21, produced in response to amino acid deficiency, in the development of GH resistance, we examined GH signaling and Igf1 mRNA levels in Fao cells cultured in amino acid-deprived medium. Despite the inhibition of Fgf21 expression by the integrated stress response inhibitor, an inhibitor of the eukaryotic initiation factor 2-activating transcription factor 4 pathway, GH resistance persisted in response to amino acid deprivation. Additionally, the introduction of FGF21 into the control medium did not impair either GH signaling or GH-induced Igf1 transcription. These data suggest that, in Fao cells, amino acid deprivation induces GH resistance independently of FGF21 activity. By shedding light on the mechanisms behind growth retardation-associated GH resistance linked to amino acid deficiencies, our findings provide valuable insights for clinicians in formulating effective treatment strategies for individuals facing these challenges.

BRCC36 associates with FLT3-ITD to regulate its protein stability and intracellular signaling in acute myeloid leukemia.

Fms-like tyrosine kinase-3 (FLT3) is a commonly mutated gene in acute myeloid leukemia (AML). The two most common mutations are the internal-tandem duplication domain (ITD) mutation and the tyrosine kinase domain (TKD) mutation. FLT3-ITD and FLT3-TKD exhibit distinct protein stability, cellular localization, and intracellular signaling. To understand the underlying mechanisms, we performed proximity labeling with TurboID to identify proteins that regulate FLT3-ITD or -TKD differently. We found that BRCA1/BRCA2-containing complex subunit 36 (BRCC36), a specific K63-linked polyubiquitin deubiquitinase, was exclusively associated with ITD, not the wild type of FLT3 and TKD. Knockdown of BRCC36 resulted in decreased signal transducers and activators of transcription 5 phosphorylation and cell proliferation in ITD cells. Consistently, treatment with thiolutin, an inhibitor of BRCC36, specifically suppressed cell proliferation and induced cell apoptosis in ITD cells. Thiolutin efficiently affected leukemia cell lines expressing FLT3-ITD cell viability and exhibited mutual synergies with quizartinib, a standard clinical medicine for AML. Furthermore, mutation of the lysine at 609 of ITD led to significant suppression of K63 polyubiquitination and decreased its stability, suggesting that K609 is a critical site for K63 ubiquitination specifically recognized by BRCC36. These data indicate that BRCC36 is a specific regulator for FLT3-ITD, which may shed light on developing a novel therapeutic approach for AML.

Advanced Interferometry with 3-D Structured Illumination Reveals the Surface Fine Structure of Complex Biospecimens.

Interference reflection microscopy (IRM) is a powerful, label-free technique to visualize the surface structure of biospecimens. However, stray light outside a focal plane obscures the surface fine structures beyond the diffraction limit (dxy ≈ 200 nm). Here, we developed an advanced interferometry approach to visualize the surface fine structure of complex biospecimens, ranging from protein assemblies to single cells. Compared to 2-D, our unique 3-D structure illumination introduced to IRM enabled successful visualization of fine structures and the dynamics of protein crystal growth under lateral (dx-y ≈ 110 nm) and axial (dx-z ≤ 5 nm) resolutions and dynamical adhesion of microtubule fiber networks with lateral resolution (dx-y ≈ 120 nm), 10 times greater than unstructured IRM (dx-y ≈ 1000 nm). Simultaneous reflection/fluorescence imaging provides new physical fingerprints for studying complex biospecimens and biological processes such as myogenic differentiation and highlights the potential use of advanced interferometry to study key nanostructures of complex biospecimens.

The IGF-Independent Role of IRS-2 in the Secretion of MMP-9 Enhances the Growth of Prostate Carcinoma Cell Line PC3.

Insulin receptor substrate-2 (IRS-2), a substrate of the insulin-like growth factor (IGF)-I receptor, is highly expressed in the prostate cancer cell line, PC3. We recently demonstrated that extracellular signal-regulated kinase (Erk1/2), a kinase downstream of IGF signaling, is activated in PC3 cells under serum starvation, and this activation can be inhibited by IRS-2 knockdown. Here, we observed that adding an IGF-I-neutralizing antibody to the culture medium inhibited the activation of Erk1/2. Suppression of Erk1/2 in IRS-2 knockdown cells was restored by the addition of a PC3 serum-free conditioned medium. In contrast, the IRS-2-silenced PC3 conditioned medium could not restore Erk1/2 activation, suggesting that IRS-2 promotes the secretion of proteins that activate the IGF signaling pathway. Furthermore, gelatin zymography analysis of the conditioned medium showed that matrix metalloproteinase-9 (MMP-9) was secreted extracellularly in an IRS-2 dependent manner when PC3 was cultured under serum starvation conditions. Moreover, MMP-9 knockdown suppressed Erk1/2 activation, DNA synthesis, and migratory activity. The IRS-2 levels were positively correlated with Gleason grade in human prostate cancer tissues. These data suggest that highly expressed IRS-2 activates IGF signaling by enabling the secretion of MMP-9, which is associated with hyperproliferation and malignancy of prostate cancer cell line, PC3.

Randomized phase II trial of chemoradiotherapy with S-1 versus combination chemotherapy with gemcitabine and S-1 as neoadjuvant treatment for resectable pancreatic cancer (JASPAC 04).

OBJECTIVE: The aim of the present study was to investigate which treatment, neoadjuvant chemoradiotherapy (NAC-RT) with S-1 or combination neoadjuvant chemotherapy with gemcitabine and S-1 (NAC-GS), is more promising as neoadjuvant treatment (NAT) for resectable pancreatic cancer in terms of effectiveness and safety. METHODS: In the NAC-RT with S-1 group, the patients received a total radiation dose of 50.4 Gy in 28 fractions with oral S-1. In the NAC-GS group, the patients received intravenous gemcitabine at a dose of 1000 mg/m2 with oral S-1 for two cycles. The primary endpoint was the 2-year progression-free survival (PFS) rate. The trial was registered with the UMIN Clinical Trial Registry as UMIN000014894. RESULTS: From April 2014 to April 2017, a total of 103 patients were enrolled. After exclusion of one patient because of ineligibility, 51 patients were included in the NAC-RT with S-1 group, and 51 patients were included in the NAC-GS group in the intention-to-treat analysis. The 2-year PFS rate was 45.0% (90% confidence interval [CI]: 33.3%-56.0%) in the NAC-RT with S-1 group and 54.9% (42.8%-65.5%) in the NAC-GS group (p = .350). The 2-year overall survival rate was 66.7% in the NAC-RT with S-1 group and 72.4% in the NAC-GS group (p = .300). Although leukopenia and neutropenia rates were significantly higher in the NAC-GS group than in the NAC-RT with S-1 group (p = .023 and p < .001), other adverse events of NAT and postoperative complications were comparable between the two groups. CONCLUSION: Both NAC-RT with S-1 and NAC-GS are considered promising treatments for resectable pancreatic cancer.

Adjuvant and neoadjuvant chemotherapy for biliary tract cancer: a review of randomized controlled trials.

The first randomized controlled trial of adjuvant chemotherapy for biliary tract cancer was reported in 2002. Since then, studies have continued, with efficacy reported for capecitabine in 2018 and S-1 in 2023. Oral fluoropyrimidines have become established as the standard of care. This article reviews the evidence from the randomized controlled trials reported to date and those that are ongoing or from which results have not yet been reported.

NEXUS trial: a multicenter phase II clinical study evaluating the efficacy and safety of the perioperative use of encorafenib, binimetinib, and cetuximab in patients with previously untreated surgically resectable BRAF V600E mutant colorectal oligometastases.

BACKGROUND: The optimal treatment strategy for resectable BRAF V600E mutant colorectal oligometastases (CRM) has not been established due to the rarity and rapid progression of the disease. Since the unresectable recurrence rate is high, development of novel perioperative therapies are warranted. On December 2020, the BEACON CRC triplet regimen of encorafenib, binimetinib, and cetuximab was approved for unresectable metastatic colorectal cancer in Japan. METHODS: The NEXUS trial is a multicenter phase II clinical study evaluating the efficacy and safety of the perioperative use of encorafenib, binimetinib, and cetuximab in patients with previously untreated surgically resectable BRAF V600E mutant CRM. The key inclusion criteria are as follows: histologically diagnosed with colorectal adeno/adenosquamous carcinoma; RAS wild-type and BRAF V600E mutation by tissue or blood; and previously untreated resectable distant metastases. The triplet regimen (encorafenib: 300 mg daily; binimetinib: 45 mg twice daily; cetuximab: 400 mg/m2, then 250 mg/m2 weekly, 28 days/cycle) is administered for 3 cycles each before and after curative resection. The primary endpoint of the study is the 1-year progression-free survival (PFS) rate and the secondary end points are the PFS, disease-free survival, overall survival, and objective response rate. The sample size is 32 patients. Endpoints in the NEXUS trial as well as integrated analysis with the nationwide registry data will be considered for seeking regulatory approval for the perioperative use of the triplet regimen. DISCUSSION: The use of the triplet regimen in the perioperative period is expected to be safe and effective in patients with resectable BRAF V600E mutant CRM. TRIAL REGISTRATION: jRCT2031220025, April. 16, 2022.

Preparation of mechanically patterned hydrogels for controlling the self-condensation of cells.

Synthetic protocols providing mechanical patterns to culture substrate are essential to control the self-condensation of cells for organoid engineering. Here, we present a protocol for preparing hydrogels with mechanical patterns. We describe steps for hydrogel synthesis, mechanical evaluation of the substrate, and time-lapse imaging of cell self-organization. This protocol will facilitate the rational design of culture substrates with mechanical patterns for the engineering of various functional organoids. For complete details on the use and execution of this protocol, please refer to Takebe et al. (2015) and Matsuzaki et al. (2014, 2022).1,2,3.

Combination Therapies with Kinase Inhibitors for Acute Myeloid Leukemia Treatment.

Targeting kinase activity is considered to be an attractive therapeutic strategy to overcome acute myeloid leukemia (AML) since aberrant activation of the kinase pathway plays a pivotal role in leukemogenesis through abnormal cell proliferation and differentiation block. Although clinical trials for kinase modulators as single agents remain scarce, combination therapies are an area of therapeutic interest. In this review, the author summarizes attractive kinase pathways for therapeutic targets and the combination strategies for these pathways. Specifically, the review focuses on combination therapies targeting the FLT3 pathways, as well as PI3K/AKT/mTOR, CDK and CHK1 pathways. From a literature review, combination therapies with the kinase inhibitors appear more promising than monotherapies with individual agents. Therefore, the development of efficient combination therapies with kinase inhibitors may result in effective therapeutic strategies for AML.

Moderate protein intake percentage in mice for maintaining metabolic health during approach to old age.

Nutritional requirements for maintaining metabolic health may vary with each life stage, such as young, middle, and old age. To investigate the appropriate ratio of nutrients, particularly proteins, for maintaining metabolic health while approaching old age, young (6-month-old) and middle-aged (16-month-old) mice were fed isocaloric diets with varying protein percentages (5%, 15%, 25%, 35%, and 45% by calorie ratio) for two months. The low-protein diet developed mild fatty liver, with middle-aged mice showing more lipids than young mice, whereas the moderate-protein diet suppressed lipid contents and lowered the levels of blood glucose and lipids. Self-organizing map (SOM) analysis revealed that plasma amino acid profiles differed depending on age and difference in protein diet and were associated with hepatic triglyceride and cholesterol levels. Results indicate that the moderate protein intake percentages (25% and 35%) are required for maintaining metabolic health in middle-aged mice, which is similar to that in young mice.

Neoadjuvant and Adjuvant Treatments for Resectable and Borderline Resectable Pancreatic Ductal Adenocarcinoma: The Current Status of Pancreatic Ductal Adenocarcinoma Treatment in Japan.

Resection is the only curative treatment for pancreatic ductal adenocarcinoma (PDAC). Although the outcome of technically resectable PDAC has improved with advances in surgery and adjuvant therapy, the 5-year survival rate remains low at 20% to 40%. More effective therapy is needed. Almost 15 years ago, the National Comprehensive Cancer Network guidelines proposed a resectability classification of PDAC based on preoperative imaging. Since then, treatment strategies for PDAC have been devised based on resectability. The standard of care for resectable PDAC is adjuvant chemotherapy after R0 resection, as shown by the results of pivotal clinical trials. With regard to neoadjuvant treatment, several recent clinical trials comparing neoadjuvant treatment with upfront resection have been conducted on resectable PDAC and borderline resectable PDAC, and the benefits and efficacy of neoadjuvant treatment for pancreatic cancer has become clearer. The significance of neoadjuvant treatment for resectable PDAC remains controversial, but in borderline resectable PDAC the efficacy of neoadjuvant treatment has been further recognised, although the standard of care has not yet been established. Several promising clinical trials for PDAC are ongoing. This review presents previous and ongoing trials of perioperative treatment for resectable and borderline resectable PDAC, focusing on the difference between Asian and Western countries.

Prognostic Impact of Margin Status in Distal Cholangiocarcinoma.

BACKGROUND: A positive ductal margin is strongly associated with poor survival in patients with distal cholangiocarcinoma. However, the significance of the radial margin status and its effect on survival are not fully clarified. METHODS: All patients with distal cholangiocarcinoma who underwent pancreatoduodenectomy between January 2000 and December 2018 at Tokai University Hospital were retrospectively analyzed. Positive margins were divided into positive ductal margin and positive radial margin. RESULTS: One hundred and eight consecutive patients with distal cholangiocarcinoma underwent pancreatoduodenectomy. Margin-negative R0 resection was performed in 85 patients (79%). Twenty-three patients (21%) had a positive resection margin (R1 resection). The 5-year survival rate and median overall survival for patients with R0 resection and those with R1 resection was 64%, 98 months and 25%, 26 months, respectively. There was a significant difference in survival between patients with R0 resection and those with R1 resection (p < 0.001). Patients with positive radial margin (n = 10) had a significantly worse outcome than those with positive ductal margin (n = 13) (p = 0.016). Univariate analysis showed that R1 resection, lymph node metastasis, tumor depth, portal vein invasion, pancreatic invasion, lymphatic invasion, and venous invasion were significant prognostic factors. Multivariate analysis confirmed that R1 resection and nodal involvement were significant independent prognostic indicators after surgical resection for distal cholangiocarcinoma. CONCLUSIONS: Positive surgical margin and nodal involvement were the strongest predictors of poor survival in patients with distal cholangiocarcinoma. Patients with a positive radial margin had a significantly worse outcome than those with a positive ductal margin.

Progression of hemolysis in a patient with hereditary spherocytosis after the second dose of COVID-19 mRNA vaccine.

Herein, we report the case of a 22-year-old woman with hereditary spherocytosis (HS) whose condition worsened after administration of the coronavirus disease 2019 (COVID-19), mRNA vaccine 'BNT162b2 Pfizer-BioNTech.' The woman had been diagnosed with HS in 2005, and her condition remained stable until February 2021. In March 2021, she received the first dose of the above vaccine and experienced pain at the injection site. After the second dose in April 2021, she developed fever and general malaise. Investigations revealed progression of hemolysis, which improved after a few days. To the best of our knowledge, this is the first report of progression of hemolysis in a patient with HS after administration of the mRNA vaccine COVID-19, BNT162b2 'Pfizer-BioNTech.'

Suspected Immune Thrombocytopenic Purpura Induced by Lenalidomide for the Treatment of Myelodysplastic Syndrome with Deletion of Chromosome 5q: A Case Report.

Lenalidomide (LEN), one of the key drugs in the treatment of myelodysplastic syndromes (MDS) with 5q deletion, as well as multiple myeloma (MM), has various immunomodulatory effects and has been associated with autoimmune diseases, including immune thrombocytopenic purpura (ITP). A 78-year-old man presented with pancytopenia and was diagnosed with MDS with 5q deletion and other chromosomal abnormalities. Two cycles of LEN therapy (one cycle: 10 mg/day for 21 days) resulted in a transient improvement in anemia, followed by MDS progression with severe thrombocytopenia (4 × 109/L) refractory to platelet transfusions. As other non-immune and alloimmune causes of transfusion-refractory thrombocytopenia were excluded, and the level of platelet-associated immunoglobulin G was extremely high compared with the level before treatment with LEN, the diagnosis of ITP was highly suspected. Despite treatment with prednisolone (PSL), eltrombopag, and repeated platelet transfusions, his platelet count did not increase, and he died of a gastrointestinal hemorrhage. Several cases of ITP induced by LEN used to treat MM had been reported, but the platelet count recovered after administration of PSL in these previous cases. However, we should be mindful of using LEN for patients with MDS because its treatment may become extremely difficult if ITP develops.