Bone marrow ring sideroblasts in hematological diseases: an analysis of consecutive 1300 samples in a single institution.

The incidence of MDS-RS in Japan has been recognized as about 5% which is lower than that in European countries. Insufficient use of iron staining tests in Japan has been noted as one conceivable factor contributing to this apparently lower prevalence. To investigate this issue, we analyzed the proportion of ring sideroblasts (RS) in 1300 bone marrow samples from patients with hematological diseases at Kitasato University Hospital, including iron staining of all samples. Sixteen of 96 patients with MDS (16.7%) were diagnosed with MDS-RS, and this accounted for 26.2% of MDS without excess blasts. Some MDS-EB (22.9%) and AML-MRC (13.8%) patients also had ≥ 15% RS. In contrast, RS were rarely found in myeloid neoplasms without dysplasia and non-myeloid diseases: only 1 in 46 (2.2%) patients with AML without dysplasia, 2 in 93 (2.2%) with MPN, and 8 in 984 (0.8%) with non-myeloid diseases had ≥ 5% RS. These results indicate that prevalence of MDS-RS in Japan may be higher than conventionally recognized and that RS are principally restricted to myelodysplastic disorders. Further multicenter studies using consecutive bone marrow samples with iron staining tests will be required to confirm our findings.

Splenectomy for Torsion of a Wandering Spleen in a Patient with Myeloproliferative Disease.

We herein report a rare case of torsion of a wandering spleen in a patient with myeloproliferative disease. A 66-year-old Japanese woman presented to our hospital with abdominal pain and a fever. She had a medical history of polycythemia and secondary myelofibrosis. Abdominal enhanced computed tomography showed an enlarged spleen without enhancement in the lower pelvic region. The clinical diagnosis was severe torsion of a wandering spleen in a patient with myeloproliferative disease, necessitating surgical intervention. Splenectomy was performed after de-rotating to revascularize the spleen. After the operation, the platelet count gradually increased, and aspirin was administered to prevent thrombosis.

The clinical outcomes of chronic myeloid leukemia patients harboring alternatively spliced BCR-ABL variants.

Objectives and importance: Tyrosine kinase inhibitors (TKIs) are indispensable for the treatment of chronic myeloid leukemia (CML). However, alternative splicing variants have been recently proposed as mechanisms of TKI resistance, although the clinical significance of these mutations remains controversial. We here present the long-term clinical courses of three CML patients harboring such unique mutations and try to assess their clinical significances. Moreover, the exon 6 frameshift presented here has been rarely reported, which may provide important information on this rare mutation. Clinical presentation: We report three cases of CML harboring an exon 7 deletion, insertion of 35 intronic nucleotides and an exon 6 frameshift, respectively. Remarkably, all patients obtained better than molecular response4.0 following administration of TKIs. Discussion and conclusion: Three CML cases highlighted an association between such splicing variants and clinical outcomes. The premature termination in the kinase domain due to these mutations likely causes conformational changes and inhibits TKI binding, but it also results in abrogating kinase activities of CML cells. Thus, the above-mentioned mutants might less affect outcomes of treatment. Noteworthy, clinically available International Scale RT-PCR system cannot distinguish kinase-active mutants from kinase-inactive mutants, which may possibly influence upon interpretation of the treatment efficacy. Clonal quantification on respective mutants could more precisely evaluate CML status in these patients. Therefore, one should realize these important splicing variants and accumulate further experiences.

Arteriolar Hyalinosis Predicts Increase in Albuminuria and GFR Decline in Normo- and Microalbuminuric Japanese Patients With Type 2 Diabetes.

OBJECTIVE: This study investigated the association between renal histology, as assessed by morphometric analysis using light (LM) and electron (EM) microscopy, and changes in urinary albumin excretion (UAE) and glomerular filtration rate (GFR) in Japanese people with type 2 diabetes in the early stages of diabetic nephropathy. RESEARCH DESIGN AND METHODS: We performed percutaneous renal biopsies in 29 patients with type 2 diabetes (22 men, mean ± SD age 49 ± 10 years and GFR 119 ± 27 mL/min/1.73 m2, with 15 normoalbuminuric [UAE <20 µg/min] and 14 microalbuminuric [UAE 20-200 µg/min]) to clarify which histological factors were associated with changes in UAE and GFR during 8.0 ± 3.5 years' follow-up. Glomerular structural changes including mesangial volume fraction [Vv(Mes/glom)] were estimated using EM, whereas the index of arteriolar hyalinosis (IAH) score was assessed by LM. Patients underwent annual measurement of GFR using iohexol injection with simultaneous urine collections for UAE. RESULTS: Vv(Mes/glom) was negatively correlated with baseline and follow-up GFR but not with UAE. The IAH score was positively correlated with UAE and negatively correlated with GFR at follow-up, but it was not correlated with either UAE or GFR at baseline. GFR at follow-up was significantly decreased from baseline in patients with IAH scores ≥2.0 and significantly lower than in patients with IAH scores <2.0. Patients with IAH scores <2.0 showed no significant change in GFR during follow-up. CONCLUSIONS: Arteriolar hyalinosis is an additional histological predictor for albuminuria increase and GFR decline in normo- and microalbuminuric Japanese people with type 2 diabetes.