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Seiichiro Katagiri,1 Nahoko Furuya,1 Daigo Akahane,1 SungGi Chi,2 Yosuke Minami,2 Yuka Harada,3 Hironori Harada,4 Akihiko Gotoh1 1Department of Hematology, Tokyo Medical University, Tokyo, Japan; 2Department of Hematology, National Cancer Center Hospital East, Chiba, Japan; 3Department of Clinical Laboratory, Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital, Tokyo, Japan; 4Laboratory of Oncology, School of Life Sciences, Tokyo University of Pharmacy and Life Sciences, Tokyo, JapanCorrespondence: Seiichiro Katagiri, Department of Hematology, Tokyo Medical University, 6-7-1 Nishishinjuku, Shinjuku-ku, Tokyo, 160-0023, Japan, Tel +81-3-3342-6111 (ext. 5895), Fax +81-3-5381-6651, Email patchsei@yahoo.co.jpAbstract: We performed sequential molecular analyses of a 75-year-old woman with de novo FLT3-ITD positive acute myeloid leukemia (AML) who had received gilteritinib therapy for 43 months. At the time of diagnosis, her karyotype was normal; however, FLT3-ITD, NPM1, DNMT3A, and IDH2 mutations were detected. She received induction therapy with daunorubicin and cytarabine and achieved hematological complete remission (HCR). After attaining HCR, she underwent consolidation therapy with azacytidine or cytarabine, aclarubicin, and granulocyte-colony stimulating factor. However, AML relapsed eight months after the first HCR. FLT3-ITD and NPM1 mutations were persistently positive, and the patient received gilteritinib therapy. Although the FLT3-ITD clone was not detected during gilteritinib treatment, a clone harboring monosomy 7 and CBL mutations emerged. Bone marrow examinations at 15, 24, and 32 months after gilteritinib treatment revealed multi-lineage blood cell dysplasia without an increase in myeloblasts. After 33 months of treatment, gilteritinib was discontinued for two months because to ileus development, and the FLT3-ITD clone was detected again. Gilteritinib treatment was restarted, and FLT3-ITD became negative. Our analysis demonstrated that: (1) hematopoiesis derived from gilteritinib-resistant clones was generated by long-term gilteritinib treatment, and (2) FLT3-ITD clones regained clonal dominance in the absence of FLT3 inhibition. These findings suggest that gilteritinib affects the selection of dominant clones during clonal hematopoiesis.Keywords: gilteritinib, FLT3-ITD, CBL, monosomy 7, clonal hematopoiesis

Yuka Saito, Hiroshi Horiguchi, Kei Mizobuchi, Satoshi Katagiri, Hisato Gunji, Tadashi Nakano Department of Ophthalmology, The Jikei University School of Medicine, Tokyo, JapanCorrespondence: Yuka Saito; Hiroshi HoriguchiDepartment of Ophthalmology, The Jikei University School of Medicine, 3-25-8 Nishi-shimbashi, Minato-ku, Tokyo, 105-8461, JapanTel +81-3-3433-1111 (ext. 3581)Fax +81-3-5378-8828Email y.saito@jikei.ac.jp; hhiro@jikei.ac.jpBackground: The reported features and effectiveness of heads-up surgery (HUS) for ophthalmic surgery include greater resolution, teaching, and significantly reduced endoillumination power.Objective: To report how to care for severe intraoperative photophobia using the HUS system during bilateral rhegmatogenous retinal detachment (RD) surgery in a patient with severe photophobia.Case Report: A man in his 50s, who had been followed up for photophobia and visual impairment underwent five ophthalmic surgeries for bilateral RD. In his early 40s, he had been referred to our hospital because of a complaint of bilateral visual impairment, including severe photophobia, approximately 2 years prior. His decimal best-corrected visual acuities were 0.7 and 0.6 in his right and left eyes, respectively. Optical coherence tomography showed diffuse thinning of the entire retinal layer in the macula of both eyes, which was considered to be a cause of the decrement of visual acuity and photophobia. Twelve years after his first visit, he noticed multiple floaters in his left eye. For RD excluding the macular area, we planned cataract and retinal surgery under retrobulbar anesthesia. However, as we could not continue retinal surgery after cataract surgery due to severe photophobia, we performed general anesthesia (GA) during the second surgery. Seventeen months after the surgery, he underwent the third surgery for RD in his right eye under GA. For RD recurring twice, we performed surgery with the HUS system under retrobulbar anesthesia for the fourth and fifth surgeries, which avoided photophobia due to the significantly reduced light stimulation of the HUS system.Conclusion: Lower light intensity achieved by the HUS system enabled us to eliminate the patient’s intraoperative discomfort. Consequently, we could perform the surgery under local anesthesia in this patient with RD who complained of severe photophobia that required GA using a conventional surgical system.Keywords: heads-up surgery, photophobia, vitrectomy, intraoperative discomfort, macular thinning

Masaki Nakamura,1 Satoshi Katagiri,1 Takaaki Hayashi,1,2 Ranko Aoyagi,1 Taiji Hasegawa,3 Akiko Kogure,3 Tomohiro Iida,3 Tadashi Nakano11Department of Ophthalmology, The Jikei University School of Medicine, Tokyo, Japan; 2Department of Ophthalmology, Katsushika Medical Center, The Jikei University School of Medicine, Tokyo, Japan; 3Department of Ophthalmology, Tokyo Women’s Medical University, Tokyo, JapanObjective: To describe longitudinal retinal changes in two cases of isolated paracentral acute middle maculopathy (PAMM).Case series: We reported two cases (64 and 67-year-old men) with isolated PAMM, who were followed-up for over 5 and 2.5 years, respectively. Both cases exhibited similar clinical natural histories. The first examinations took place several days after onset, with funduscopy showing that both cases exhibited paracentral scotoma with good visual acuity and small gray lesions, while optical coherence tomography (OCT) showed the presence of a hyperreflective band that ranged from the inner plexiform layer to the outer plexiform layer (OPL). The lesions became unremarkable within 1 month. The hyperreflective band also became unremarkable and was limited to the inner nuclear layer (INL) within 1 month, with the band disappearing within several months. Subsequently, OCT showed there was a thin and irregular INL and OPL, an excavated change of the inner retinal surface, along with outer nuclear layer (ONL) thickening. After several years, OCT angiography demonstrated normal flow of macular capillaries in the superficial capillary plexus, and decreased flow in the lesion with dilation of the capillaries around the area in the deep capillary plexus (DCP). Focal serous retinal detachment (SRD) occurred in one case after 4–5 years.Conclusion: Our findings indicated that long-term retinal changes in PAMM resulted in excavation of the inner retinal surface, INL thinning, ONL thickening and abnormal vasculature, especially in the DCP. Focal SRD may be a rare complication that can present at 4 years after onset.Keywords: paracentral acute middle maculopathy, optical coherence tomography angiography, serous retinal detachment

Junko H Ohyashiki,1 Kazushige Ohtsuki,1 Izuru Mizoguchi,2 Takayuki Yoshimoto,2 Seiichiro Katagiri,3 Tomohiro Umezu,1,4 Kazuma Ohyashiki3,4 1Department of Molecular Oncology, Institute of Medical Science, 2Department of Immunoregulation, Institute of Medical Science, 3Department of Hematology, 4Department of Molecular Science, Tokyo Medical University, Tokyo, Japan Background: A subset of patients with chronic myeloid leukemia (CML) can sustain a complete molecular response after discontinuing imatinib mesylate (IM). We focused on microRNAs (miRNAs), with the aim of finding a molecular biomarker to discriminate which patients can safely and successfully discontinue IM use. Methods: To identify miRNAs that showed altered expression in patients who had discontinued IM (STOP-IM group), we first screened miRNA expression of peripheral blood mononuclear cells by using a TaqMan miRNA array on samples from five unselected patients from the STOP-IM group, seven CML patients receiving IM (IM group), and five healthy volunteers. We then performed miRNA quantification in 49 CML patients with deep molecular response. Mann–Whitney U and chi-square tests were used to determine statistical significance for comparisons between the control (healthy volunteers) and test groups (STOP-IM and IM groups). Multiple groups were compared by one-way analysis of variance. Results: Downregulation of miR-148b was noted in patients in the STOP-IM group and in a subset of the IM group. We then subdivided the IM patients into two groups: one with downregulated miR-148b expression (IM-1; less than the cut-off value) and the other without downregulated miR-148b expression (IM-2; greater than the cut-off value). The number of patients who had a sustained stable molecular response was significantly lower in IM-2 group. This group also had a significantly lower percentage of natural killer cells. Conclusion: Downregulated miR-148 may contribute to immune surveillance in STOP-IM patients and may therefore have potential as additive information in managing CML patients undergoing treatment with IM. Keywords: chronic myeloid leukemia, imatinib mesylate, discontinuation, miR-148b