Feasibility of ovarian stimulation for fertility preservation during and after blinatumomab treatment for Ph-negative B-cell acute lymphoblastic leukemia.

It is challenging to preserve the fertility of female patients with B-cell acute lymphoblastic leukemia (B-ALL) before allogeneic hematopoietic stem cell transplantation (allo-HSCT) while maintaining treatment intensity. We report two cases of female patients with Philadelphia chromosome-negative (Ph -) B-ALL whose oocytes were retrieved after controlled ovarian stimulation during and after blinatumomab treatment. The first patient was a 30-year-old woman with relapsed Ph-B-ALL who received prednisolone (PSL) and cytoreductive chemotherapy with cyclophosphamide, vincristine, doxorubicin, and dexamethasone, followed by three courses of blinatumomab bridging to allo-HSCT. Ovarian stimulation was performed twice during blinatumomab administration, and two oocytes were retrieved during each course. The second patient was a 26-year-old woman with newly diagnosed Ph-B-ALL who received PSL, one course of conventional chemotherapy, and one course of high-dose methotrexate and cytarabine followed by two courses of blinatumomab bridging to allo-HSCT. Immediately after completion of the first course of blinatumomab, ovarian stimulation was performed, and three oocytes were retrieved. Use of a 2-week rest period enabled ovarian stimulation and oocyte retrieval to be performed without delaying treatment. Blinatumomab may be an option for preserving fertility while maintaining treatment intensity.

ILF2 enhances the DNA cytosine deaminase activity of tumor mutator APOBEC3B in multiple myeloma cells.

DNA cytosine deaminase APOBEC3B (A3B) is an endogenous source of mutations in many human cancers, including multiple myeloma. A3B proteins form catalytically inactive high molecular mass (HMM) complexes in nuclei, however, the regulatory mechanisms of A3B deaminase activity in HMM complexes are still unclear. Here, we performed mass spectrometry analysis of A3B-interacting proteins from nuclear extracts of myeloma cell lines and identified 30 putative interacting proteins. These proteins are involved in RNA metabolism, including RNA binding, mRNA splicing, translation, and regulation of gene expression. Except for SAFB, these proteins interact with A3B in an RNA-dependent manner. Most of these interacting proteins are detected in A3B HMM complexes by density gradient sedimentation assays. We focused on two interacting proteins, ILF2 and SAFB. We found that overexpressed ILF2 enhanced the deaminase activity of A3B by 30%, while SAFB did not. Additionally, siRNA-mediated knockdown of ILF2 suppressed A3B deaminase activity by 30% in HEK293T cell lysates. Based on these findings, we conclude that ILF2 can interact with A3B and enhance its deaminase activity in HMM complexes.

[BCR-ABL1-positive myelodysplastic syndrome with neutropenia and anemia treated successfully with imatinib mesylate].

An 81-year-old female was referred to our hospital with progressive neutropenia and anemia of unknown etiology. We performed a bone marrow biopsy which was notable for hypercellularity, multinucleated megakaryocytes and hypo-granular neutrophils with 2.6% blasts. A diagnosis of myelodysplastic syndrome with multilineage dysplasia (MDS-MLD) was made. Karyotype analysis revealed a t (9;22)(q34;q11.2) BCR-ABL1 fusion with no additional chromosomal abnormalities. BCR-ABL1 was also detected in transcripts from peripheral blood cells as well as in polynuclear leukocytes via FISH. Within one year, her peripheral blood neutrophil count had declined to 403/µl; further analysis was notable for increasing dysplasia including enlarged platelets and hypo-granular neutrophils. Platelet counts gradually increased over time and reached 100×104/µl. A second bone marrow examination revealed similar cell morphology and the BCR-ABL1 translocation. Her condition deteriorated and blood transfusions were required. Treatment with low doses of the tyrosine kinase inhibitor (TKI), imatinib mesylate (100 mg), was initiated. Thereafter, both the neutropenia and anemia resolved gradually, platelet counts returned to normal levels, and dysplasia eventually disappeared. Detection of the BCR-ABL fusion in mRNA decreased to < 0.0007% (IS%) after 16 months of treatment. Several cases of BCR-ABL1-positive myelodysplastic syndrome treated with TKIs have been reported. Our results suggest that complete hematologic recovery in response to imatinib mesylate suggests a critical role for the BCR-ABL1 fusion in the pathogenesis of this disease.

Experimental verification of a two-sensor acoustic intensity measurement in lossy ducts.

Two-sensor method proposed by Fusco et al. ["Two-sensor power measurements in lossy ducts," J. Acoust. Soc. Am. 91, 2229-2235 (1992)] is a novel technique that determines acoustic intensity of a gas column in a wide duct from measurements of pressure based on the boundary layer approximation. For further development of this method, its validity is experimentally tested through comparison with the direct method measuring the pressure and the velocity simultaneously, and its formulation is modified to include the narrow duct range where the duct radius is smaller than the viscous boundary layer thickness of the gas. It is shown that the modified two-sensor method enables quick and accurate evaluation of the acoustic intensity seamlessly from narrow to wide duct ranges.

Acoustic intensity measurement in a narrow duct by a two-sensor method.

The use of two pressure sensors [Fusco et al., J. Acoust. Soc. Am. 91, 2229 (1992)] makes it possible to determine the acoustic intensity of a gas column in a duct, but the application of this method was limited to wide ducts. In this letter, the formulation of the method is modified to include narrow ducts where the duct radius is as small as the viscous boundary layer thickness of the gas. The validity of this method is shown by comparison with the direct measurements of the pressure and velocity.

Determination of a response function of a thermocouple using a short acoustic pulse.

This paper reports on an experimental technique to determine a response function of a thermocouple using a short acoustic pulse wave. A pulse of 10 ms is generated in a tube filled with 1 bar helium gas. The temperature is measured using the thermocouple. The reference temperature is deduced from the measured pressure on the basis of a laminar oscillating flow theory. The response function of the thermocouple is obtained as a function of frequency below 50 Hz through a comparison between the measured and reference temperatures.

Experimental demonstration of thermoacoustic energy conversion in a resonator.

Using thermoacoustic energy conversions, both amplification and damping of acoustic intensity are demonstrated. A differentially heated regenerator is installed near the velocity node of the resonator and thereby a high specific acoustic impedance and a traveling wave phase are obtained. It is shown that the gain of acoustic intensity resulting from the traveling wave energy conversion reaches 1.7 in a positive temperature gradient and 0.3 in a negative gradient. When the regenerator is replaced with a stack, it is found that the gain reaches 2.3, exceeding the temperature ratio (=1.9) of both ends of the stack. This is brought about by the addition of standing wave energy conversion. The present results would contribute to the development of new acoustic devices using thermoacoustic energy conversion.