Takanori Toyama

Telomerase activity and telomere length as prognostic factors of adult T-cell leukemia

For the oncogenesis of many malignancies, it is crucial to prevent the shortening of the telomeres by the action of telomerase. In this study, clinical data and disease outcomes were analyzed in conjunction with the telomerase activity (TA) and telomere length (TL) of peripheral blood mononuclear cells. The study was carried out in 22 patients with adult T-cell leukemia (ATL) (7 chronic and 15 acute types) and in 13 asymptomatic human T-lymphotropic virus type 1 (HTLV-1) carriers. The mean values of TA in acute and chronic type patients were 13.8 and 1.6 total product generated (TPG) units, respectively, as determined by telomeric repeat amplification assays. The mean TA values in HTLV-1 carriers and healthy volunteers were 1.8 and 0.7 TPG, respectively. The mean TA value in acute type patients was significantly higher than in the three other subject groups. The mean TL values in patients with acute and chronic types were 5.39 and 4.38 Kb, respectively, while the mean TL values in HTLV-1 carriers and healthy volunteers were 7.69 and 7.06 Kb, respectively. The mean TL values in all ATL patients and in non-ATL subjects were 5.2 and 7.3 Kb, respectively. The former value is significantly shorter than the latter (p < 0.01). Neither TA nor TL of ATL cells showed any significant association with the number of ATL cells, serum soluble interleukin-2 receptor, or serum lactate dehydrogenase in the peripheral blood of acute type patients. This suggests that the levels of TA and TL did not reflect the ATL tumor load. The median survival period of acute ATL patients with high TA and shortened TL was 0.47 years, however, which was significantly shorter than that of acute ATL patients with low TA and normal TL (4.21 years) (p < 0.002). These data suggest that high TA and shortened TL were associated with poorer prognosis, and that TA and TL may be novel markers for the prognosis of ATL patients.

Clinical significance of CD45RO expression on peripheral blood mononuclear cells in HTLV-I-infected individuals

The phenotype of peripheral blood mononuclear cells (PBMC) was examined in 13 healthy volunteers, 26 HTLV‐I carriers, and 58 ATL patients (22 smouldering, five chronic, 24 acute, and seven lymphoma type). The percentage of CD4+, CD25+, CD28+ and CD45RO+ cells in the PBMC of the chronic and acute type patients was significantly higher than that of the volunteers, whereas the percentage of CD8+ and CD45RA+ cells in these patients was significantly low. The histogram for CD45RO fluorescence intensity (FI) revealed two patterns: pattern A consisted of CD45RO+ cells with high FI (CD45ROhigh) and intermediate FI (CD45ROint). Pattern B consisted exclusively of CD45ROhigh. Pattern A was evident in all volunteers. The percentage of subjects showing pattern B was increased in an order that reflected disease progression. In the patients with pattern A, the CD45ROint cells were CD4+ and CD8−, and the FI of CD2, CD3, and Fas within the CD45ROint cells appeared to be lower than that within the CD45ROhigh cells. The acute type patients with pattern A had a significantly longer survival curve than that of these patients with pattern B. These results suggest that the presence of CD45ROint cells may be related to protection against disease progression in HTLV‐I‐infected individuals.

A case of pemphigus vulgaris accompanied by multiple myeloma

Pemphigus is a mucocutaneous intraepithelial blistering disease caused by autoantibodies to epithelial cell adhesion molecules (desmoglein). The association between pemphigus and malignant neoplasm is well recognized. We present the case of a 62‐year‐old woman with pemphigus vulgaris accompanied by multiple myeloma. To the best of our knowledge, this is the first report of a case of pemphigus vulgaris concomitant with multiple myeloma. From the results of immunoblotting using normal human epidermal extracts and indirect immunofluorescence using rat bladder sections, and her clinical manifestations, our case does not seem to be one of paraneoplastic pemphigus.

Effects of mogamulizumab in adult T-cell leukemia/lymphoma in clinical practice.

The efficacy of mogamulizumab in adult T‐cell leukemia/lymphoma (ATLL) was reported in a previous phase 2 study. Compared with patients in clinical trials, however, most patients in real‐life settings have demonstrated worse outcomes.

Early/prefibrotic primary myelofibrosis in patients who were initially diagnosed with essential thrombocythemia

A new entity, namely early/prefibrotic primary myelofibrosis (PMF), was introduced as a subtype of PMF in the 2016 revised World Health Organization (WHO) criteria for myeloproliferative neoplasms (MPN). It was diagnosed based on histopathological features of bone marrow (BM) biopsy specimens together with clinical parameters [leukocytosis, anemia, elevated lactate dehydrogenase (LDH) values, and splenomegaly]. The aim of this study was to evaluate the prevalence of early/prefibrotic PMF in patients who were previously diagnosed with ET, and to compare clinical features at diagnosis and outcomes between early/prefibrotic PMF and essential thrombocythemia (ET) patients. BM biopsy samples obtained at the time of ET diagnosis were available in 42 patients. Sample reevaluation according to the 2016 revised WHO criteria revealed that early/prefibrotic PMF accounted for 14% of patients who were previously diagnosed with ET, which was comparable to the rates in previous reports. Compared to patients with ET, patients with early/prefibrotic PMF had higher LDH values and higher frequencies of splenomegaly. Overall, myelofibrosis-free and acute myeloid leukemia-free survivals were comparable between the 2 groups. Accurate diagnosis is required to clarify the clinical features of Japanese ET patients.