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Background/Aim: Bone marrow metastasis (BMM) of gastric cancer (GC) is complicated by disseminated intravascular coagulation syndrome (DIC), which is more prominent in poorly differentiated carcinoma. This is one of the first case reports of a slowly progressing BMM of GC after approximately 1 year of follow-up without treatment. Case Report: A 72-year-old woman underwent total gastrectomy and splenectomy for GC in February 2012. The pathological diagnosis was that of a moderately differentiated adenocarcinoma. Five years later in December 2017, she developed anemia; however, its cause remained unknown. Due to worsening of the anemia, the patient visited the Kakogawa Central City Hospital in October 2018. Bone marrow biopsy revealed an infiltration of caudal type homeobox 2-positive cancer cells, and our diagnosis was BMM of GC. There was no DIC. The incidence of BMM is high in well- or moderately differentiated breast cancer but rarely causes DIC. Conclusion: As with breast cancer, in moderately differentiated cancer cells, BMM of GC may progress slowly after the appearance of symptoms without causing DIC.

We recently reported the translocation of the immunoglobulin (Ig) light chain κ locus gene with a possible tumor suppressor gene, TFL, in transformed follicular lymphoma. However, the functional significance in cell transformation remains to be elucidated. Here, we first identified two gene products, P58TFL and P36TFL, derived by alternative splicing. The expression was prominent in normal human lymphocytes but defective in some leukemia/lymphoma cell lines. Overexpression of either protein in a mouse pro-B cell line, Ba/F3, and a human leukemia cell line, Jurkat, inhibited G1 to S phase progression through suppression of retinoblastoma protein (Rb) phosphorylation. The dominant gene product, P58TFL, colocalized with mRNA-processing body markers, eukaryotic translation initiation factor 2C and DCP1 decapping-enzyme homolog A, but not with a stress granule maker, T-cell intracellular antigen 1, in the cytoplasm. Taken together with the unique CCCH-type zinc finger motif, the present study suggests that P58TFL could play an important role in the regulation of cell growth through posttranscriptional modification of cell cycle regulators, at least partially, upstream of Rb. (Mol Cancer Res 2009;7(6):880–9)

Supplementary Data from Inhibition of G1 to S Phase Progression by a Novel Zinc Finger Protein P58TFL at P-bodies

Background/Aim: Pulmonary arterial intimal sarcoma (PAIS) is a rare malignant soft tissue tumor that is difficult to differentiate from pulmonary thromboembolism (PTE). Therefore, pre-operative diagnosis is often difficult. However, recent advances in fluorodeoxyglucose positron emission tomography (FDG-PET) have enabled the use of standardized uptake values (SUVs) for the differential diagnosis of PAIS from PTE, and the frequency of diagnosis of PAIS has increased. Here, we report a case of PAIS that was difficult to differentiate from PTE despite using FDG-PET. Case Report: A 40-year-old woman presented with gradually worsening exertional dyspnea. Contrast-enhanced computed tomography (CT) revealed lesions with poor enhancement in the right lateral basal pulmonary artery. FDG-PET/CT did not reveal any tumor or thrombosis in other areas. Cytological evaluation using a right ventricular catheter did not lead to a definitive diagnosis. Because the patient did not respond to anticoagulation, we performed pulmonary artery endarterectomy. Pathological examination of the pulmonary artery tumor revealed a mucinous tumor with an edematous stroma and spindle-shaped tumor-cell proliferation, which confirmed the diagnosis of PAIS. However, FDG/PET demonstrated a low SUV of 3.4. Conclusion: Some PAISs with low cellular densities and high mucous tissue proportions have SUVs similar to those in PTE. In patients with low FDG uptake, if PAIS is suspected based on other objective findings, additional exploration using highly invasive tests or surgical procedures specific to PAIS is warranted.

Background: This study aimed to evaluate the usefulness of the Cancer and Aging Research Group (CARG) predictive tool in older Japanese patients with cancer. Methods: Patients aged 65 years or older with solid tumors treated with new anticancer regimens in Kakogawa Central City Hospital between April 2016 and March 2019 were included. Grade 3 or higher risks of developing chemotherapy-related adverse events (CRAEs) were calculated using the tool (low-, intermediate-, or high-risk scores). The association between grade 3–5 CRAE incidence during the first course of each regimen and the calculated risk or the patient characteristics was evaluated. The difference in the incidences of CRAEs between the groups was evaluated by Fisher’s exact test. Results: This study examined 76 patients (mean age: 71 (65–82) years). The incidence of grade 3–5 CRAE was 38%, 55%, and 76% in patients classified as low, medium, and high CARG risk scores (p = 0.035), and the incidence of severe non-hematological toxicities was 4%, 31%, and 52% (p < 0.01), respectively. Eastern Cooperative Oncology Group performance status and age were not associated with chemotherapy toxicity. Conclusions: The CARG predictive tool was valid, suggesting its usefulness in optimizing chemotherapy outcomes in older patients with cancer.

Objective Chemotherapy-induced peripheral neuropathy (CIPN) is a common adverse event experienced by cancer patients. In general, CIPN is evaluated subjectively based on patient self-assessment or clinician-reported scales; evidence supporting the utility and validity of quantitative sensory tests (QST) is lacking in this patient population. The aim of this study was to objectively assess CIPN of lower extremities by QSTs, and to evaluate the concordance between QSTs and subjective assessments. Methods In this prospective cohort study, outpatients with cancer receiving chemotherapy were recruited at a single university hospital. We assessed CIPN at the lower extremities at baseline and three months after baseline. The QSTs were performed by applying a monofilament and a tuning fork to determine touch and vibration thresholds, respectively, at the affected site. Subjective assessments were performed based on the visual analog scale (VAS) and the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) toxicity grade. Kappa coefficients were calculated to evaluate the concordance between QSTs and subjective assessments. Results After exclusion and drop-outs during follow-up, nineteen patients were included in the analysis. The prevalence of patients with abnormal sensation was 37% based on QSTs, 32% based on the VAS, and 14% based on CTCAE grading, respectively. Kappa coefficients were 0.32 between QSTs and VAS, and 0.28 between QSTs and CTCAE. Conclusions The concordance rates between quantitative and subjective assessments were low. CIPN should be assessed using both quantitative and subjective assessments.

Chemotherapy-induced peripheral neuropathy (CIPN) frequently occurs in lymphoma patients receiving R-CHOP, a drug combination therapy. Although severe CIPN may lead to reduction and/or discontinuation of the medication, predictive factors of CIPN have not been investigated sufficiently to date. We performed a retrospective exploratory research to determine associations between prevalence of severe CIPN and socio-demographic data, health characteristics, and medical conditions such as anemia at initial diagnosis. Forty patients (indolent lymphoma, n = 9; diffuse large B-cell lymphoma; n = 31) received R-CHOP therapy from September 2009 to July 2014. The median age of patients was 58 years (range = 27–76 years). Statistical analy-ses were applied to the patients, who were divided into two groups: mild CIPN (no symptoms or grade 1 according to the CTCAE version 3.0 program) and severe CIPN patients (grade 2 or higher). Forward stepwise logistic regression analyses were performed using the following variables: sex, BMI, BSA, hyperglycemia, malnutrition, and anemia. Severe CIPN occurred in seven patients (17.5%). Gender and anemia remained following the stepwise procedure, and anemia predicted severe CIPN significantly (OR = 19.45, 95% confi-dence interval = 1.52–171.12). Our study suggests that anemia at initial diagnosis could be a predictive factor of R-CHOP-induced CIPN.

Chromosomal rearrangements involving the MECOM locus, which consists of two genes MDS1 and EVI1 located at 3q26.2, are found in different types of myeloid malignancies [1,2]. Among these, the t(3;1...

Sinusoidal obstruction syndrome (SOS) is a lethal complication after hematopoietic stem cell transplantation (HSCT). Defibrotide (DF) is the only drug internationally recommended for SOS treatment in Western countries. Recombinant human soluble thrombomodulin (rhTM), which is promising for the treatment of patients with disseminated intravascular coagulation, is also reported to be potentially effective for SOS. To clarify the safety and efficacy of DF and rhTM, we conducted a retrospective survey of these agents in Japan. Data from 65 patients who underwent allogeneic HSCT and received DF (n = 24) or rhTM (n = 41) for SOS treatment were collected. The complete response rates for SOS on day 100 were 50% and 54% in the DF and rhTM groups, respectively. The 100-day overall survival rates were 50% in the DF group, and 48% in the rhTM group. Several severe hemorrhagic adverse events were observed in one patient in the DF group and five patients in the rhTM group. The main causes of death were SOS-related death, and no patient died of direct adverse events of DF or rhTM. Our results suggest that rhTM, as well as DF, can be effective as a novel treatment option for SOS.

Immune reconstitution affects clinical outcomes after allogeneic hematopoietic stem cell transplantation (HSCT), and it has been suggested that lymphocyte recovery affects survival after HSCT. However, few studies have examined lymphocyte recovery in Asian patients who received mycophenolate mofetil (MMF) prophylaxis for graft-versus-host disease. We retrospectively evaluated early lymphocyte recovery after HSCT among Japanese adults who received MMF prophylaxis. Patients were divided into two groups according to their median absolute lymphocyte count (ALC) on day 28 after HSCT as follows: the “low ALC group” (≤ 0.22 × 109 cells/L) and the “high ALC group” (> 0.22 × 109 cells/L). With a median follow-up of 317 days, the high ALC group showed significantly better overall survival than the low ALC group (at 1 year: 62 vs. 46%, P = 0.02). The high ALC group also tended to have better non-relapse mortality than the low ALC group (at 1 year: 13 vs. 23%, P = 0.08). There was no significant difference in relapse rate between the high and low ALC groups (at 1 year: 29 vs. 35%, P = 0.2). We conclude that among Japanese patients who received MMF prophylaxis, ALC on day 28 after HSCT was effective in predicting overall survival and non-relapse mortality.

Mycophenolate mofetil (MMF) is increasingly used among Japanese patients undergoing allogeneic hematopoietic stem cell transplantation (allo-SCT). Because pharmacokinetic data for MMF in the Asian population are limited, we conducted this investigation. Intravenous MMF (1000 mg/dose) was administered to 10 patients along with cyclosporine or tacrolimus for 10 days after allo-SCT; it was administered every 8 h in peripheral blood stem cell- and bone marrow-transplanted patients, and every 12 h in cord blood-transplanted patients. MMF was administered orally at the same dose from day 11. Plasma concentrations of mycophenolic acid (MPA) were measured by high-performance liquid chromatography. The MPA AUC0 − tau was 31.9 ± 3.4, 26.2 ± 2.4, and 21.0 ± 2.2 µg*h/mL, the mean Ctrough was 0.25, 0.35, and 0.37 µg/mL, and the Cmax was 10.8, 9.2, and 5.5 µg/mL on days 2, 9, and 16, respectively. The AUC0 − tau and Cmax were significantly higher after intravenous MMF dosing than after oral MMF dosing. All patients exhibited successful neutrophil engraftments in a median time of 18 days. Grade II acute graft-versus-host disease (GvHD) of the skin was observed in two patients, and one patient developed limited chronic GvHD. Individual cases of transient and curable grade III oral mucositis and diarrhea were observed; however, MMF was not discontinued. No other severe complications or infections were observed. Intravenously administered MMF was safe and possibly effective in achieving higher MPA plasma concentrations for GvHD prophylaxis after allo-SCT in Japanese patients.

No optimum treatment of iatrogenic immunodeficiency-associated lymphoproliferative disorders due to methotrexate in patients with rheumatoid arthritis (MTX-LPD) has yet been established, although MTX withdrawal is known to have a substantial effect on tumor regression. Here, we retrospectively analyzed 20 cases of MTX-LPD. Tumor shrinkage occurred in 18 of 20 cases, but only following MTX withdrawal. This tumor regression ratio was considerably better than in previous reports, and appeared due to longer "watchful waiting." Lymphocyte recovery at 2 weeks after MTX withdrawal was significantly higher in cases with tumor regression in 1 month than in those without tumor regression (p = 0.001). Median time to maximal efficacy after MTX cessation in cases without chemotherapy was 12 weeks (range 2-76). In conclusion, watchful waiting for a longer period after MTX cessation with observation of early lymphocyte recovery and uninterrupted continuation of other anti-rheumatoid drugs may be an acceptable management plan for MTX-LPD.

Rhabdomyolysis is characterized by a marked elevation of the creatine kinase (CK) levels and myoglobinuria, thus leading to renal dysfunction. Various viruses or bacteria can be etiologic agents, but mycosis has only rarely been reported to be a cause of rhabdomyolysis. In this report, we describe an adolescent male with acute myeloid leukemia who underwent allogeneic bone marrow transplantation and thereafter developed rhabdomyolysis and Candida parapsilosis fungemia almost at the same time. Following treatment for C. parapsilosis, the transaminase and CK levels both satisfactorily decreased. This case illustrates that C. parapsilosis infection may be a causative agent of rhabdomyolysis in immunocompromised patients.

Various chemotherapeutic agents used in patients with hematopoietic malignancy cause serious side effects, including myelosuppression and immunosuppression. Immunosuppression makes patients more susceptible to infection, resulting in an increased risk of infectious complications, including the development of severe septicemia that may be life-threatening. It is necessary for dental staff to be familiar with an appropriate protocol in such cases and to share information about the chemotherapy with a hematologist. To verify the effectiveness of our dental intervention protocol, we conducted a prospective study on the incidence of complications for each myelosuppressive grade of chemotherapy in patients with hematopoietic malignancy. We compared the incidence of complications between treatment P (patients who finished all the dental treatments according to the protocol) and treatment Q (patients who did not) per grade (A, B, C, D) and incidence of systemic or oral findings. We also compared the incidence of oral complication related to the residual teeth between first chemo (patients who were undergoing chemotherapy for the first time) and prior chemo (not the first time). There were significant differences in inflammatory complications between treatment P and treatment Q. We found that both systemic and oral inflammatory complications increased with higher-grade myelosuppressive chemotherapy. Additionally, there was a significant difference between the incidence of oral complications related to the residual teeth between first chemo and prior chemo. Complete implementation of the dental intervention protocol was associated with fewer oral and systemic infectious and inflammatory complications in patients with hematopoietic malignancies undergoing chemotherapy. The incidence of oral and systemic complications also increased with grade of chemotherapy. These results support the validity of our dental intervention protocol. We should pay close attention to the oral state of de novo hematopoietic malignancy patients.

Background Human herpesvirus 6 (HHV-6) encephalitis is a known life-threatening complication following allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, few studies have focused on the occurrence of HHV-6 encephalitis in patients receiving mycophenolate mofetil (MMF) combined with a calcineurin inhibitor as prophylaxis for graft-versus-host disease (GVHD). This study aimed to investigate the impact of MMF administered for GVHD prophylaxis in the occurrence of HHV-6 encephalitis after allo-HSCT and the characteristics of this condition. Methods and results We retrospectively analyzed 73 patients who underwent allo-HSCT (83 transplants) at our hospital between April 2010 and December 2015. MMF (2-3 g/d) was administered along with a calcineurin inhibitor. Seven patients (8.0%) developed encephalitis due to HHV-6. The median period from allo-HSCT to the onset of HHV-6 encephalitis was 23 days (range, 17-98 days). The cumulative incidence of HHV-6 encephalitis on day 100 after treatment was 12% and 6% in patients who underwent cord blood transplantation (CBT) and non-CBT (ie, bone marrow transplantation and peripheral blood stem cell transplantation), respectively (P = 0.344). Neurological symptoms of encephalitis were more severe in non-CBT cases than those in CBT cases. All patients diagnosed with HHV-6 encephalitis were treated with ganciclovir or foscarnet. None of the enrolled patients died from HHV-6 encephalitis. Conclusions Mycophenolate mofetil may have the potential to increase the frequency of severe HHV-6 encephalitis in patients undergoing CBT and non-CBT. Thus, MMF should be administered with caution, and patients should be monitored closely for HHV-6 encephalitis even those who did not undergo CBT.

myeloperoxidase and α -naphthyl butyrate esterase staining. Surface marker analyses with three-color fl ow cytometry by CD45/side scatter gating revealed that immature cells (76.9% of all bone marrow cells) were positive ( 20%) for CD4 (25.3%), CD13 (86.7%), CD33 (100.0%) and CD34 (99.2%). Considering cytogenetic abnormalities and MLL rearrangements described below, we made a diagnosis of AML with a variant MLL translocation in the World Health Organization classification, or AML M4 in the French – American – British classification. Induction therapy with idarubicin and cytosine arabinoside was started, and the patient achieved a hematological complete remission (CR). However, she suffered from severe pneumonia and heart failure, and died of multiple organ failure 2 months after the initial diagnosis. Chromosome analysis of the bone marrow cells at the initial diagnosis showed 50,XX, 4, 6, 8,?t(10;11)(p12;q14)

Chromosomal abnormalities of intravascular large B-cell lymphoma (IVLBCL), a rare form of extranodal diffuse large B-cell lymphoma, have been described in only a small number of cases. A 59-year-old female presented with pancytopenia and splenomegaly. Bone marrow was normocellular with 30.4% abnormal large lymphoid cells that were positive for CD5, CD19, CD20, HLA-DR and λ chain. Bone marrow biopsy showed intrasinusoidal infiltration of large lymphoid cells. G-banding and spectral karyotyping of the bone marrow cells demonstrated a complex karyotype as follows : 48,XX,-8,+r(11),+12,del(12)(p?) ×2,+18,der(19)(19?::p13 → qter),der(21)t(8;21)(q11.2;p11.2). Fluorescence in situ hybridization on interphase nuclei revealed three signals of CCND1 at 11q13, but two signals of BIRC3 at 11q22 and MLL at 11q23, indicating that r(11) contained CCND1. Together with other reported cases, our results indicate that the gain of 11q as well as trisomy 18 may be among the recurrent chromosomal aberrations in IVLBCL. Furthermore, an additional ring chromosome 11 could be a novel mechanism leading to the gain of 11q.

To test the feasibility of mycophenolate mofetil (MMF) for graft-versus-host disease (GVHD) prophylaxis in Japanese patients, we conducted two multicenter prospective phase II trials of allogeneic hematopoietic stem-cell transplantation (HSCT) from HLA-matched related donors (MRD group) with MMF and cyclosporine or HLA 7–8/8 allele-matched unrelated bone-marrow donors (URD group) with MMF and tacrolimus. The cumulative incidences of grade II–IV acute GVHD on day 100, which was the primary endpoint in these trials, were 45.0% (90% CI 25.8–62.5) and 25.8% (90% CI 13.9–39.5) in the MRD (n = 20) and URD (n = 31) groups, respectively. The rates of 3-year overall survival and non-relapse mortality were 80.0 and 15.0% in the MRD group and 74.2 and 6.5% in the URD group, respectively. GVHD prophylaxis with MMF may lead to a lower incidence of severe mucositis and faster neutrophil engraftment compared to that with methotrexate. A pharmacokinetics study of mycophenolic acid (MPA) showed that a relatively higher plasma concentration of MPA was associated with a lower incidence of acute GVHD. In conclusion, the results of these studies suggest that GVHD prophylaxis with MMF may be useful as an alternative in Japanese patients who may benefit from faster engraftment or less severe mucositis after allogeneic HSCT.

Background In T-cell acute lymphoblastic leukemia/lymphoma (T-ALL/LBL), activating mutations of NOTCH1 are observed in more than 50% of cases, whereas the t(7;9)(q34;q34) involving NOTCH1 at 9q34 and TRB@ at 7q34 is an extremely rare but recurrent translocation. Patient A 41-year-old male with a large mediastinal mass, pleural effusion, and lymphadenopathy was diagnosed as having T-LBL. Lymphoma cells were positive for CD4, CD8, CD2, CD3, CD5, CD7, CD10, and TdT. Results G-banding and spectral karyotyping of pleural effusion cells showed 47,XY,dup(1)(q21q32),t(7;9)(q34;q34),+20. Genomic polymerase chain reaction (PCR) revealed that the 5' end of TRB@ J1-5 was connected with the middle of NOTCH1 exon 25 (434 bp downstream from its 5' end) in a 'head-to-head' configuration on the der(9)t(7;9), although nine extra bases were inserted between the two genes. Reverse transcription-PCR confirmed expression of the TRB@/NOTCH1 fusion transcripts. Similarly, the 5' end of J1-5 was fused to the shortened exon 25 with nine extra bases. The NOTCH1 breakpoint in exon 25 was very close to transcription start sites of deleted Notch1 in murine T-ALL. Conclusions The TRB@/NOTCH1 fusion gene with a NOTCH1 breakpoint in exon 25, which has not previously been detected in four other reported cases with t(7;9), could lead to aberrant expression of the truncated NOTCH1 by TRB@ enhancer elements. The resultant NOTCH1 receptor deleting most of the extracellular domain may be implicated in the pathogenesis of T-LBL by ligand-independent, constitutive activation of the NOTCH1 pathway, suggesting avenues for future therapy with γ-secretase inhibitors.

Objectives: The t(9;11)(p22;p15) is a very rare but recurrent translocation in acute myeloid leukemia (AML) and chronic myeloid leukemia (CML) blast crisis. The translocation results in a fusion gene between NUP98 at 11p15 and PSIP1 encoding two transcriptional coactivators, p52 and p75, at 9p22. Here, we describe the first case of myelodysplastic syndrome (MDS) with t(9;11)(p22;p15). Patient: A 64-yr-old woman presented pancytopenia, trilineage dysplasia, and 9.2% blasts in the bone marrow, indicating the diagnosis of MDS. Results: G-banding and spectral karyotyping showed 46,XX,t(9;11)(p22;p15)[20]. Reverse transcription-polymerase chain reaction (RT-PCR) and nucleotide sequencing detected four types of NUP98/PSIP1-p52 and two types of NUP98/PSIP1-p75 fusion transcripts. Essentially, the NUP98 exon 12 or exon 11 by alternative splicing was fused in-frame with the PSIP1 exon 8. Real-time quantitative (RQ) PCR for NUP98/PSIP1/GAPDH demonstrated a 4-log decrease after cord blood transplantation and a 2-log increase at relapse. Conclusions: The fusion genes combining NUP98 exon 11/12 with PSIP1 exon 8, which have never been detected in other AML/CML cases, may be implicated in the pathogenesis of MDS. Furthermore, RQ-PCR for NUP98/PSIP1 could be useful to monitor minimal residual disease.

Myelodysplastic syndromes (MDS) with pure red cell aplasia (PRCA) have been shown to be a rare form of MDS. A 35-year-old man presented with pancytopenia: hemoglobin 59 g/L, reticulocytes 2 × 10(9)/L, platelets 33 × 10(9)/L, and leukocytes 1.8 × 10(9)/L with 1% blasts. Bone marrow was hypercellular with 50.4% myeloid cells, 0.0% erythroblasts, 25.4% basophils, and 5.6% myeloblasts. Dysplastic changes including pseudo-Pelger-Huët anomaly of neutrophils and mononuclear micromegakaryocytes were found. Immunohistochemistry with glycophorin C confirmed erythroid aplasia. Cytogenetic analysis showed 46,XY,i(17)(q10)[18]/47,XY,+8[2]. Considering two reported cases, these findings indicate that isolated i(17q) may be implicated in the pathogenesis of MDS with PRCA as a recurrent cytogenetic aberration.

Pure erythroid leukemia (PEL) is an extremely rare disorder characterized by neoplastic proliferation of immature erythroblasts. A 66-year-old man, who had received chemoradiotherapy for hypopharyngeal cancer, was admitted because of pancytopenia. Bone marrow was infiltrated with 81% proerythroblasts positive for CD71 and CD235a. An increased number of macrophages with active hemophagocytosis was also present. Chromosome analysis showed hypodiploid complex abnormalities. The patient died of progressive disease despite induction chemotherapy. Erythroblastic infiltration into the liver and hemophagocytosis in the spleen were found at autopsy. Therapy-related PEL with hemophagocytic syndrome and hepatic infiltration of PEL has never been reported.

Hematopoietic stem/progenitor cells (HSPCs) are released from the bone marrow to the circulation by the cytokine, granulocyte colony-stimulating factor, via sympathetic nervous system (SNS)–mediated osteoblast suppression. Because the orientation of HSPCs in their osteoblastic niche is reported to be guided by [Ca2+], we speculated on a cooperation between the calcium-regulating hormones and SNS in the regulation of HSPC trafficking. Here, we present the severe impairment of granulocyte colony-stimulating factor–induced osteoblast suppression and subsequent HSPC mobilization in vitamin D receptor (VDR)–deficient mice. In osteoblasts, functional VDR possessing, at least in part, a transcriptional activity, was specifically induced by β2-adrenergic receptor (AR) agonists. While β2-AR agonists transiently increased mRNA expression of Vdr and its downstream gene, Rankl, 1α,25-dihydroxyvitamin-D3 sustained the β2-AR–induced Rankl expression at high level by stabilizing VDR protein. These data suggest that VDR is essential for durable β2-AR signaling in the stem cell niche. Our study demonstrates not only a novel function of VDR as a critical modulator of HSPC trafficking, but also the presence of a SNS-mediated, bone-remodeling mechanism through VDR. VDR contributes to brain-bone-blood integration in an unanticipated way distinct from other classical calcium-regulating hormones.

Background We examined the relationship between the improved physical activity by early rehabilitation and the duration of hospitalization among patients after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Methods Thirteen allo-HSCT patients with myeloablative conditioning regimens (group A) and 13 patients with nonmyeloablative conditioning regimens (group B) were assessed retrospectively in this study. All patients received physical exercise immediately after neutrophil engraftment at the class 10,000 bioclean room (class 10,000). The mean daily steps at class 10,000 were measured as a substitute for the amount of physical activity, and the duration of hospitalization as one of the clinical outcomes. Results The degree of physical activity showed a negative correlation with the duration of hospitalization in group A (r = −.71; P = .0071), regardless of complications such as acute graft-versus-host disease, infections, and cytomegalovirus reactivation. However, there was no significant association in group B (r = .09; P = .77). Conclusion The improved physical activity through early rehabilitation may be an independent, favorable prognostic factor for allo-HSCT patients with myeloablative conditioning regimens.

We describe here a novel unbalanced whole-arm translocation der(3;10)(q10;q10) in a 58-year-old man with acute monocytic leukemia. Bone marrow was massively infiltrated with 22.2% monoblasts, 55.4% promonocytes, and 5.6% monocytes. These monocytic cells were positive for myeloperoxidase and alpha-naphthyl butyrate esterase staining. Surface marker analysis revealed that they were positive for CD4, CD13, CD33, CD56, and HLA-DR but negative for CD14 and CD34. Chromosome analysis of the bone marrow cells showed 46,XY,+3,der(3;10)(q10;q10)[18]/46,XY[2]. Spectral karyotyping confirmed der(3;10)(q10;q10) as a sole structural abnormality. By acquisition of a normal chromosome 3 but not a chromosome 10, the der(3;10)(q10;q10) resulted in trisomy 3q and monosomy 10p. The +3,der(3;10)(q10;q10) is thought to play a crucial role in the pathogenesis of acute monocytic leukemia because of the gain of 3q or the loss of 10p.

We recently reported the translocation of the immunoglobulin (Ig) light chain κ locus gene with a possible tumor suppressor gene, TFL, in transformed follicular lymphoma. However, the functional significance in cell transformation remains to be elucidated. Here, we first identified two gene products, P58TFL and P36TFL, derived by alternative splicing. The expression was prominent in normal human lymphocytes but defective in some leukemia/lymphoma cell lines. Overexpression of either protein in a mouse pro-B cell line, Ba/F3, and a human leukemia cell line, Jurkat, inhibited G1 to S phase progression through suppression of retinoblastoma protein (Rb) phosphorylation. The dominant gene product, P58TFL, colocalized with mRNA-processing body markers, eukaryotic translation initiation factor 2C and DCP1 decapping-enzyme homolog A, but not with a stress granule maker, T-cell intracellular antigen 1, in the cytoplasm. Taken together with the unique CCCH-type zinc finger motif, the present study suggests that P58TFL could play an important role in the regulation of cell growth through posttranscriptional modification of cell cycle regulators, at least partially, upstream of Rb. (Mol Cancer Res 2009;7(6):880–9)

We describe here two cases of myelodysplastic syndrome (MDS) with a novel unbalanced translocation der(5;19)(p10;q10). Both patients had complex karyotypes including der(5;19) accompanied by an extra chromosome 19, resulting in deletion of the whole long arm of chromosome 5. Furthermore, these patients presented several common clinical and hematological characteristics: MDS subtypes as refractory anemia with excess of blasts (RAEB)-1 or RAEB-2, marked anemia and thrombocytopenia without neutropenia, leukoerythroblastosis, trilineage dysplasia with prominent dyserythropoiesis, CD7 expression in blasts, and association with abnormalities of chromosomes 6, 17 and 18. These findings indicate that der(5;19)(p10;q10) may play a crucial role in the pathogenesis of high-risk MDS as a rare but recurrent translocation.

For better clinical outcomes of mycophenolate mofetil (MMF) in allogeneic hematopoietic stem cell transplantation (alloSCT), higher mycophenolic acid (MPA) plasma levels are proposed to be desirable. Here, we investigate the optimal MMF dosing strategy based on pharmacokinetic studies in 20 Japanese alloSCT patients. The first 11 patients received MMF twice daily at an escalated dose from 15 mg/kg, according to real-time pharmacokinetic monitoring of the total MPA area under the curve (AUC). In the subsequent nine patients, MMF was given at a fixed dose of 1,000 mg three-times daily. The pharmacokinetic data revealed that the dose escalation in each individual did not always increase the AUC. In contrast, the increase of dosing frequency could statistically keep higher MPA plasma levels, as reflected in higher concentration at steady state (C (ss)) or trough value (C (trough)). There was no symptomatic adverse event in both groups. These results suggest that MMF administration of every 8 h after alloSCT would be better to maintain higher MPA plasma levels than that of every 12 h even in the same daily dose. Further studies are necessary to confirm the clinical benefit of MMF to prevent graft failure, as well as severe aGVHD.

Constitutional trisomy 8 mosaicism (CT8M) has been considered to be the first mutation in multistep carcinogenesis. We describe the case of a 38-year-old woman with a normal phenotype who developed to acute monocytic leukemia with a novel t(8;18)(q13;q21). Chromosome analysis and spectral karyotyping showed 47,XX,+8,t(8;18)(q13;q21)[20]. Fluorescence in situ hybridization (FISH) demonstrated that the breakpoint at 18q21 was centromeric to the MALT1 and BCL2 genes. FISH also revealed that trisomy 8 was detected in buccal mucosa cells, indicating that trisomy 8 was a constitutional abnormality. These results suggest that t(8;18)(q13;q21) had a crucial role in the development of leukemia as the second mutation following CT8M.

Rhabdomyolysis is characterized by a marked elevation of the creatine kinase (CK) levels and myoglobinuria, thus leading to renal dysfunction. Various viruses or bacteria can be etiologic agents, but mycosis has only rarely been reported to be a cause of rhabdomyolysis. In this report, we describe an adolescent male with acute myeloid leukemia who underwent allogeneic bone marrow transplantation and thereafter developed rhabdomyolysis and Candida parapsilosis fungemia almost at the same time. Following treatment for C. parapsilosis, the transaminase and CK levels both satisfactorily decreased. This case illustrates that C. parapsilosis infection may be a causative agent of rhabdomyolysis in immunocompromised patients.