ABSTRACT Prolonged hospitalization is often required due to conditions such as chemotherapy. For patients with prolonged hospitalizations during their educational years, uninterrupted education and support for university admission or career development are important considerations. However, internet‐based communication devices have made it possible for patients to attend online classes and to participate in university entrance interviews remotely, even while hospitalized. This article highlights the utility of internet‐based communication devices as an educational tool for young people that require prolonged hospitalization.

DNA ligase IV (LIG4) is essential for DNA double-strand break (DSB) repair. Hypomorphic LIG4 variants cause LIG4 syndrome, characterized by growth disturbance, increased radiosensitivity, predisposition to malignancies, adaptive immunodeficiency and inflammatory conditions. Most of these manifestations are recapitulated in hypomorphic LIG4 mutant mice. However, no model mice with defective DSB repair have consistently exhibited inflammation. Here, we have generated mutant mice carrying the LIG4 missense variant, p.W447C, found in a patient with LIG4 syndrome. Lig4W447C/W447C mice showed functional defects of LIGIV and manifested growth retardation, increased radiosensitivity, and life-threatening intestinal inflammation under severe adaptive immunodeficiency. The inflammation was dependent on lymphocytes and characterized by marked infiltration of Th1 cells and macrophages, along with elevated expression of IFN-γ-inducible genes. When Ifng was deleted, Th2 and Th17 instead of Th1 cells drove the inflammation. Single-cell RNA-seq analyses with TCR repertoire revealed that T cells from Lig4W447C/W447C mice preferentially used proximal Vα and Jα segments in V regions of TCRα chains and exhibited expansion of several clonotypes, a substantial portion of which were CD4 T cells expressing IFN-γ. Thus, our hypomorphic Lig4 mutant mice represent a unique model for studying Th1-skewed intestinal inflammation under severe adaptive immunodeficiency.

Cytogenetic of COH-DHL1 and COH-THL1 HGBCL-DH-BCL2(-BCL6) cell line models (A-D); In vivo secondary Ighv gene rearrangements in BCR-less murine lambda-MYC lymphomas (E-J)

Dysregulation of DNA double-strand break (DSB) repair leads to adaptive immunodeficiency, whereas the remaining lymphocytes are aberrantly activated and provoke inflammations. However, no model mice were available to consistently manifest inflammation under defective DSB repair. We generated mutant mice carrying a missense mutation p.W447C in the gene encoding DNA ligase IV (LIG4), critical for DSB repair. Lig4W447C/W447C mice showed growth retardation and severe intestinal inflammations under adaptive immunodeficiency. The inflammations were featured by marked infiltration of T helper type 1 (Th1) cells and macrophages and was dependent on lymphocytes. When Ifng was deleted, Th2 and Th17 instead of Th1 cells drove the inflammations. Lig4W447C/W447C mice showed expansion of oligoclonal T cells with T cell receptor α repertoire skewed towards more proximal 3’ V and 5’ J gene segments. Thus, our novel hypomorphic Lig4 mutant mice show that defective DSB repair leads to Th1-dependent intestinal inflammations under severe adaptive immunodeficiency. ### Competing Interest Statement The authors have declared no competing interest. Grant-in-Aid for Transformative Research Areas, JP22H05182, JP22H05187, JP22H05187 Grant-in-Aid for Scientific Research (B) Grant-in-Aid for Scientific Research (C) Grant-in-Aid for Scientific Research on Innovative Areas Grant-in-Aid for Early-Career Scientists Grant-in-Aid for Research Activity Start-up, JP23K19487 Grant-in-Aid for JSPS Fellows Grant-in-Aid for Exploratory Research, JP17K19568, JP21K19384, JP23K18222 Wakayama Medical University Special Grant-in-Aid for Research Projects, K23TS03

Erdheim-Chester disease (ECD) is a rare form of non-Langerhans histiocytic disease with no established therapeutic approach. Here we report a case of ECD treated with molecular targeted therapy. A 61-year-old woman diagnosed with ECD with BRAFV600E mutation received combination therapy with a BRAF inhibitor (dabrafenib) and MEK inhibitor (trametinib). Grade 1 fever and liver injury were detected early in the course of treatment, leading to temporary interruption. However, treatment was successfully resumed with concomitant administration of prednisolone. The BRAFV600E allele frequency in plasma cell-free DNA became negative at 8 weeks of treatment, and PET/CT confirmed a partial metabolic response at 24 weeks. Recent studies have demonstrated the benefit of molecular targeted therapy for ECD. However, due to the rarity of ECD, treatment guidelines remain poorly defined, with limited guidance on indicators of treatment efficacy, optimal treatment duration, and criteria for treatment cessation. In the case of our patient as well, it will be necessary to consider the duration of treatment while carefully monitoring the clinical course.

BACKGROUND:In recent years, letermovir has been routinely used for cytomegalovirus (CMV) infection prophylaxis in patients receiving allogeneic hematopoietic stem-cell transplantation (HSCT). The reduction effect of letermovir on CMV infection rates and the impact on survival have been studied, but other potential benefits of letermovir remain underexplored. METHODS:This retrospective study included patients who underwent first-time allogeneic HSCT between October 2013 and August 2023. We compared the length of hospital stay between eras before and after the introduction of letermovir ("nonletermovir group" and "letermovir group," respectively). Secondary outcomes included clinically significant CMV infection rates and hospitalization costs. RESULTS:A total of 59 patients were analyzed in the nonletermovir group and 65 patients in the letermovir group. The median length of hospital stay was 51 days in the nonletermovir group and 42 days in the letermovir group (p < 0.001). Among standard-risk disease patients, the letermovir group also had significantly shorter hospital stays (p = 0.0048). Additionally, the cumulative incidence of clinically significant CMV infection and grade II-IV acute graft-versus-host disease were both lower in the letermovir group. Hospitalization costs were not significantly different between the two groups. CONCLUSION:The length of hospital stays after HSCT was observed to be shorter following the introduction of letermovir in this study. This reduction in hospital stays did not decrease hospitalization costs in relation to allogeneic HSCT, but it may alleviate the burden on both patients and healthcare providers.

Obinutuzumab-induced acute thrombocytopenia is characterized by a rapid decrease in the platelet count after administration. The underlying mechanisms remain unclear. However, we present novel laboratory findings related to its pathophysiology. A 65-year-old woman with follicular lymphoma developed acute thrombocytopenia within 24 hours after obinutuzumab administration. Laboratory results showed features resembling acute immune thrombocytopenic purpura, including an elevated immature platelet fraction, mildly increased thrombopoietin levels, elevated platelet-associated IgG, and refractory to platelet transfusion. Our case and her laboratory findings suggest that increased platelet consumption might be involved in the development of obinutuzumab-induced acute thrombocytopenia.

This phase 2 study evaluated the impact of pegfilgrastim, a single-dose, long-acting granulocyte colony-stimulating factor, on the steady-state mobilization of hematopoietic stem cells into peripheral blood in patients with multiple myeloma (MM) or malignant lymphoma (ML). Efficacy and safety, along with CD34-positive cell mobilization outcomes were assessed in patients with MM, who were randomly assigned to pegfilgrastim (n = 30) or daily filgrastim (n = 31), and ML (pegfilgrastim only, n = 13) cohorts. In the MM cohort, CD34-positive cell counts ≥ 2 × 106/kg were achieved in 100% of patients in the pegfilgrastim group and 96.7% in the filgrastim group (difference: 3.3%; 80% confidence interval: −0.9–7.5%), demonstrating the non-inferiority of pegfilgrastim to filgrastim. All patients in the ML cohort achieved ≥ 2 × 106/kg CD34-positive cell counts. The plerixafor administration rates in the MM cohort were 50.0% and 63.3% in the pegfilgrastim and filgrastim groups, respectively, and 91.7% in the ML cohort. There were no major differences in safety measures between the two groups. Although the sample size was small, particularly in the ML cohort, a single dose of pegfilgrastim demonstrated comparable efficacy and safety to daily doses of filgrastim, indicating its potential for clinical use while reducing patient burden. Trial Registration: jRCT2011210029, NCT05007652.

Early disease progression, including histological transformation, can occur in follicular lymphoma, but tumor heterogeneity makes comparison difficult. We analyzed cell-free DNA from 30 patients with follicular lymphoma to assess cell-free DNA concentration and gene mutations. Mutational profiles were also examined in 16 cases using DNA from formalin-fixed, paraffin-embedded tissue samples. Cell-free DNA concentrations were higher in cases with histological transformation. Both the number of mutations per patient and the number of mutated genes were greater in cell-free DNA than in formalin-fixed, paraffin-embedded tissue-derived DNA. Notably, TP53 mutations were more frequently detected in cell-free DNA. CIITA mutations were more commonly observed in cases with a low frequency of somatic hypermutation in VH genes. Cell-free DNA analysis in follicular lymphoma may become a complementary approach, overcoming the limitations of assessing disease status from single biopsy sites. Further studies will examine the usefulness of cell-free DNA in predicting disease progression in follicular lymphoma.

Introduction Paroxysmal nocturnal hemoglobinuria (PNH) is a rare, life-threatening hematologic disorder caused by clonal expansion of hematopoietic stem cells (HSCs) with somatic PIGA mutations. These mutations lead to the loss of GPI-anchored proteins, such as CD55 and CD59, on red blood cells, resulting in complement-mediated hemolysis. Although complement inhibitors like eculizumab provide symptomatic relief, a substantial proportion of patients, particularly in East Asia (including Japan), exhibit a limited therapeutic response due to bone marrow failure (BMF), either present at diagnosis or developing later, such as aplastic anemia (AA) or myelodysplastic syndromes (MDS). This highlights the need for curative approaches. While PIGA-mutated (PNH-type) and wild-type HSCs coexist, the former preferentially expand. Immune escape due to GPI-AP deficiency has been proposed, yet mechanisms driving clonal dominance and ineffective hematopoiesis remain unclear (Murakami et al., Blood 2002; Hanaoka et al., Blood 2006). Although PNH-specific mutations have been hypothesized, only alterations in genes like TET2, ASXL1, and JAK2—commonly found in AA, MDS, or clonal hematopoiesis—have been reported (Shen et al., J Clin Invest 2014), and no PNH-specific mutations have been conclusively identified. Induced pluripotent stem cells (iPSCs) derived from patients offer a useful platform for studying rare diseases with limited sample availability, allowing functional gene analysis and disease modeling. We therefore generated iPSCs from PNH patients to explore gene alterations involved in PNH-associated BMF (PNH-BMF). Methods Five PNH patients with BMF were enrolled. PNH-iPSCs and matched wild-type N-iPSCs were established by reprogramming mononuclear hematopoietic cells from each patient. These iPSCs were differentiated into hematopoietic stem/progenitor cells (HSPCs), and their differentiation and proliferation were evaluated. PIGA mutations in PNH-iPSCs were corrected using CRISPR/Cas9. Whole-genome sequencing (WGS) was performed on PNH-iPSCs, N-iPSCs, and normal somatic cells from the same patients. PNH-specific variants were defined based on stopgain, frameshift, and splice-site mutations, as well as nonsynonymous SNVs annotated as pathogenic or likely pathogenic in AlphaMissense and ClinVar. Candidate variants were cross-referenced with curated databases of hematopoiesis-associated genes potentially linked to hematopoietic dysfunction. Results Among the five patients, one had hypoplastic marrow and four had normoplastic marrow. Median neutrophil counts, hemoglobin, and platelet counts were 1.6 × 10⁹/L, 8.4 g/dL, and 97 × 10⁹/L, respectively. Median proportions of PNH-type erythrocytes and granulocytes were 24.3% and 67.2%, suggesting an underlying BMF tendency. Hematopoietic dysfunction was reproduced in the PNH-iPSC model. Correction of PIGA mutations failed to fully restore normal hematopoiesis, suggesting the involvement of additional pathogenic factors. WGS analysis was successfully completed in four patients. Multiple PNH clone-specific somatic mutations were identified in all cases. In two patients, variants involved known hematopoiesis-related genes such as DNMT3A and ASXL1. One patient progressed to MDS during follow-up, indicating a possible genotype–phenotype correlation. The remaining two patients harbored novel mutations not previously reported to associate with hematopoietic dysfunction. Although not known to directly promote proliferation or survival, database analyses suggested these mutations may alter HSC biology—through impaired quiescence, lineage skewing, or disrupted interactions with the bone marrow niche. No shared mutations were observed across patients, supporting the notion that the pathogenesis of PNH-associated BMF is genetically heterogeneous. Conclusions We successfully established matched PNH- and N-iPSC lines from four patients and modeled hematopoietic abnormalities in vitro. Limited hematopoietic recovery following PIGA correction suggests the involvement of additional genetic factors. WGS identified PNH clone–specific somatic mutations in all cases, involving both known and novel genes potentially affecting hematopoiesis. These findings support the genetic heterogeneity of PNH-BMF and highlight the potential value of precision medicine in future treatment strategies. Ongoing CRISPR/Cas9-mediated knock-in experiments targeting selected genes in N-iPSCs are underway to assess their pathogenic relevance.

The B-cell receptor (BCR) is critical for mature B-cell lymphomas (BCL), serving as a therapeutic target. We show that high-grade BCLs with MYC and BCL2 rearrangements [HGBCL-double-hit (DH)-BCL2] predominantly exhibit immunoglobulin heavy (IGH) chain silencing, leading to BCR shutdown. IGH-silenced HGBCL-DH-BCL2 (IGHUND) tumors differ from IGH+ counterparts in germinal center (GC) zone programs, MYC expression, and immune infiltrate. Whereas IGH+ HGBCL-DH-BCL2 tumors favor IGM/IG-κ expression, IGHUND counterparts complete IGH isotype switching and IG-λ rearrangements. IGHUND lymphomas retain productive IGHV rearrangements and require IGH for optimal fitness. BCR silencing, caused by accelerated IGH turnover and reduced IGH expression, precedes HGBCL-DH-BCL2 onset, inducing RAG1/2-dependent IG light chain editing and facilitating t(8;22)/IGL::MYC translocations. IGHUND HGBCL-DH-BCL2 models exhibit reduced sensitivity to the CD79B-targeting antibody-drug conjugate polatuzumab vedotin. Collectively, HGBCL-DH-BCL2 commonly arises from isotype-switched t(14;18)+ GC B cells, which edit IG light chains, fueling intraclonal diversification, BCR extinction, and t(8;22) while maintaining IGH dependence, with clinical implications. SIGNIFICANCE:These findings link BCR silencing in IGH isotype-switched t(14;18)+ GC B cells to RAG1/2 expression, which triggers IG light chain editing and predisposes to IGL::MYC translocations, promoting HGBCL. In HGBCL with MYC and BCL2 rearrangements, BCR silencing protects from polatuzumab vedotin killing. See related commentary by Shevchenko and Hodson, p. 284.

Automated hematology analyzers are routinely used to assess blood cell counts and leukocyte differentials. However, the accuracy of assessing neutrophil percentages with automated hematology analyzers in patients undergoing chemotherapy has not been examined. In this study, the correlation between neutrophil percentages calculated by automated hematology analyzers and those obtained through manual microscopic examinations by laboratory technicians was investigated on the day of chemotherapy initiation in 125 patients receiving CHOP-based chemotherapy for malignant lymphoma. Peripheral blood counts and 5-part leukocyte differential percentages were analyzed using the Sysmex XE-5000 system. An examination of 797 samples from each chemotherapy course showed a favorable correlation between the two methods (Pearson’s r = 0.917). However, this correlation significantly diminished in samples when the bone marrow nucleated cell count was ≤ 50 × 109/L or granulocyte colony-stimulating factors were administered in previous chemotherapy courses (r = 0.881 and 0.886, respectively). Furthermore, a tendency towards a weaker correlation was noted when the percentage of immature neutrophils exceeded 3

Introduction Although the prognosis of follicular lymphoma (FL) is improved, that of transformed FL (trFL) is still poor. Distinguishing between FL and trFL is crucial for determining appropriate treatment strategies. However, due to tumor heterogeneity, a single-site biopsy may be insufficient to differentiate between FL and trFL. Cell-free DNA (cfDNA) contains tumor-derived DNA and has the potential to capture heterogeneous tumor profiles. We compared mutation profiles in cfDNA and tissue-derived DNA from FL patients and evaluated the utility of cfDNA in assessing transformation. Materials and methods This is a prospective, non-interventional, observational study. Patients with newly diagnosed or relapsed FL were enrolled. Clinical trFL was defined based on previously reported criteria. cfDNA was extracted from the 33 patients. Mutations in 33 genes associated with FL transformation were analyzed using targeted-capture sequencing. Results The study included 33 patients with FL, of whom 13 were trFL (5 clinically diagnosed and 8 histologically diagnosed). The median age at cfDNA collection was 71 (36-93) years, and 15 were males. Twenty-two patients were classified as Ann Arbor stage III/IV. Twenty-three patients underwent PET scans within three months before and after cfDNA sample collection, with a median SUV max of 15. There were no significant differences in age, gender, PS, FLIPI, or stage between FL and trFL groups. The amount of cfDNA in trFL was higher than that of FL (median:23.2 ng/mL in trFL vs 4.2 ng/mL in FL, p<0.001). Even after adjusting for the metabolic tumor volume of PET scans, the amount of cfDNA was significantly higher in trFL than in FL (p=0.017). The optimal cut-off value for distinguishing between FL and trFL based on cfDNA amount was determined to be 16.6 ng/mL using ROC curve analysis. Targeted sequencing was performed on cfDNA from 30 patients, and for 16 of these patients, DNA extracted from FFPE tissue biopsies was also analyzed using targeted sequencing. At least one somatic mutation was detected in all cfDNA samples, with a mean of 11.7 mutations, whereas a mean of 2.1 mutations were detected per FFPE sample. One hundred mutations were detected in cfDNA, 13 of which were also identified in FFPE-derived DNA. Among mutations in cfDNA, TP53 was most frequent (76%), followed by CREBBP in 60%, KMT2D in 60%, CARD11 in 43%, CIITA in 26%. In FFPE-derived DNA, CREBBP (37%) and KMT2D (18%) were also frequent. However, TP53 was detected in only one case (6%) from FFPE-derived DNA, and the same TP53 mutation was also observed in the cfDNA of that case. Although there was no significant difference in the detection rate of TP53 mutations between FL and trFL, the TP53 variant allele frequency (VAF) in cfDNA was significantly higher in histologically trFL compared to other FL (p=0.0472). Interestingly, a TP53 G245D substitution was observed in 14 samples (63%). Discussion In cfDNA, TP53 mutations were detected even in cases lacking TP53 mutations in FFPE samples. The higher VAF of TP53 in trFL suggests that cfDNA analysis can detect subclonal TP53 mutations and may enable early identification of transformation.

Introduction Immune-mediated thrombotic thrombocytopenic purpura (iTTP) is a fatal disease characterized by severe deficiency of the von Willebrand factor-cleaving protease ADAMTS13. We reported that the cause of sudden death in patients with iTTP in the early period after starting treatment was mainly fatal arrhythmia, pathologically representing diffuse microthrombi and ischemic changes in the heart tissue. However, few reports have evaluated the details of the chest symptoms at onset in patients with iTTP. Recent reports have shown that neutrophil extracellular traps (NETs) are associated with thrombogenesis during iTTP. Currently, positive chest findings have been considered as indicators in patients with iTTP. This study aimed to describe the relationship between positive chest findings at presentation and acute TTP-related mortality rates and evaluate the correlation between TTP-related death and NET-associated markers in the Japanese iTTP registry. Methods Questionnaire surveys were administered in the treating physicians. Patients diagnosed with iTTP in hospitals across Japan between 2010 and 2023 were enrolled. We collected chest symptoms and electrocardiogram (ECG) based on the Minnesota Code Classification System and transthoracic echocardiogram (TTE) findings based on Recommendations for a Standardized Report for Adult Transthoracic Echocardiography at onset using questionnaire surveys. We measured troponin I, myeloperoxidase (MPO), and histone DNA complexes by enzyme-linked immunosorbent assay using frozen plasma at onset preserved at our institution. The overall survival (OS) rate was estimated using the Kaplan-Meier method. To compare the mortality rates, continuous variables were divided into two groups based on the median or cutoff value for clinical use. We used the Log-rank and Gray's tests to compare the mortality rates and cumulative incidence function, respectively. Statistical significance was defined as p < 0.05. Results This study enrolled 125 patients with iTTP. The median follow-up period was 1026 days. ECG was performed in 100 patients, of which 40 had abnormal findings. TTE was performed in 32 patients at disease onset, of which 19 had abnormal findings. Troponin T and I levels were measured in 56 patients at each institution; the positive values were 40. The 5-year OS rate was 83.6%. Eighty samples were evaluated for troponin I, MPO, and histone DNA complex levels. Median troponin I, MPO, and histone DNA complex levels were 9.342 pg/mL (IQR; <4.4-76.56), 252.5 ng/mL (IQR; 148.6-608.3), and 2.128 mU (IQR; 0.802-6.231), respectively. During the study period, 15 patients died, of which five were TTP-related deaths; sudden cardiac death (N=4) and alveolar hemorrhage (N=1). In the cases of non-TTP-related death, the main cause of death was pneumonia (N=3), followed by cancer (N=2). Three patients with TTP-related death had ECG findings; atrial fibrillation (N=1), left bundle branch block (N=1), and sinus tachycardia (N=1). However, none of these patients presented with chest symptoms. The median survival days between TTP-related and non-TTP-related deaths were significantly different (six and 65 days, respectively, p<0.005). Between cases of survivors, TTP-related deaths, and non-TTP-related deaths, there were no significant differences in troponin I (p=0.173), MPO (p=0.116), and histone DNA complex levels (p=0.06), respectively. Based on the presence or absence of physiological findings, there were no statistically significant differences in the ECG (p=0.174) or TTE (p=0.336) findings in the mortality rate of TTP-related deaths. Based on median levels, there were no statistically significant differences in troponin I (p=0.14) and MPO levels (p=0.30), but there was a statistically significant difference in histone DNA complex levels (p=0.04) in the mortality rate of TTP-related death. Conclusions These results suggest that chest symptoms and physiological and biochemical findings at disease onset do not contribute to acute mortality. Paradoxically, even patients with abnormal findings at initial presentation can be treated by appropriate therapeutic interventions. Higher MPO and histone DNA complex levels may contribute to TTP-related death. However, further studies are required to confirm these findings.

TAFRO syndrome is a systemic inflammatory disease characterized by thrombocytopenia and anasarca. It results from hyperinflammation and produces severe cytokine storms. Severe acute respiratory syndrome coronavirus 2, which led to the coronavirus disease 2019 (COVID-19) pandemic, also causes cytokine storms. COVID-19 was reported to be associated with various immune-related manifestations, including multisystem inflammatory syndrome, hemophagocytic syndrome, vasculitis, and immune thrombocytopenia. Although the pathogenesis and complications of COVID-19 have not been fully elucidated, the pathogeneses of excessive immunoreaction after COVID-19 and TAFRO syndrome both involve cytokine storms. Since the COVID-19 pandemic, there have been a few case reports about the onset of TAFRO syndrome after COVID-19 or COVID-19 vaccination. Castleman disease also presents with excessive cytokine production. We reviewed the literature about the association between TAFRO syndrome or Castleman disease and COVID-19 or vaccination against it. While the similarities and differences between the pathogeneses of TAFRO syndrome and COVID-19 have not been investigated previously, the cytokines and genetic factors associated with TAFRO syndrome and COVID-19 were reviewed by examining case reports. Investigation of TAFRO-like manifestations after COVID-19 or vaccination against COVID-19 may contribute to understanding the pathogenesis of TAFRO syndrome.

C-Mannosyl tryptophan (CMW), a unique glycosylated amino acid, is considered to be produced by degradation of C-mannosylated proteins in living organism. Although protein C-mannosylation is involved in the folding and secretion of substrate proteins, the pathophysiological function in the hematological system is still unclear. This study aimed to assess CMW in the human hematological disorders. The serum CMW levels of 94 healthy Japanese workers were quantified using hydrophilic interaction liquid chromatography. Platelet count was positively correlated with serum CMW levels. The clinical significance of CMW in thrombocytosis of myeloproliferative neoplasms (T-MPN) including essential thrombocythemia (ET) were investigated. The serum CMW levels of the 34 patients with T-MPN who presented with thrombocytosis were significantly higher than those of the 52 patients with control who had other hematological disorders. In patients with T-MPN, serum CMW levels were inversely correlated with anemia, which was related to myelofibrosis (MF). Bone marrow biopsy samples were obtained from 18 patients with ET, and serum CMW levels were simultaneously measured. Twelve patients with bone marrow fibrosis had significantly higher CMW levels than 6 patients without bone marrow fibrosis. Collectively, these results suggested that CMW could be a novel biomarker to predict MF progression in T-MPN.

IGLL5 is shown to be located near super-enhancer (SE) in B-cell tumors, and this gene is frequently mutated and a target of translocation in B-cell tumors. These results suggest roles of the IGLL5 in tumorigenesis; however, its functional properties have been unclear. We found that two mature B-cell lymphoma cell lines expressed IGLL5 mRNA with Cλ1 segment. JQ1 treatment resulted in down-expression of IGLL5, indicating that IGLL5 is controlled by SE. IGLL5 knockdown induced cell death with down-expression of MYC. Our results suggested that IGLL5 might have a role in survival of mature B-cell tumors and involvement in MYC expression. (100 words)