Dear Dr. Preffer, The colorful cover figure shown on the Clinical Cytometry Volume to first bear your name as Editor-in-Chief [Volume 82B, Number 1, January 2012] contains numerous bivariate dot –plots demonstrating, embarrassingly, one of the most annoying and irritating characteristics you always try to avoid and have been heard many times to preach wildly against! Specifically, rather than ‘X’ & ‘Y’ axes labeled with meaningful antibody-fluorochrome combinations, these plots show bewildering ‘FL1,’ ‘FL2’ and ‘FL3’labels! I sincerely hope you can do a far better job at correcting such data presentation, in the future. I have additional concerns with the depicted orientation of Forward and Side Scatter as well, but will leave that for another time. Sincerely, Frederic I. Preffer Editor-in-Chief*, * Boston, MAJanuary 24, 2012.
The meeting provides scientific updates and practical information on topics of interest to clinical cytometrists and hematopathologists.Sessions at this meeting will cover minimal residual disease, hematopathology, bone marrow analysis, and biomarkers in clinical research, as well as interesting case study interpretations, and luncheon workshops.The course, which follows the meeting, provides in-depth training for practical analysis of clinical specimens by flow cytometry.Prior to the meeting, on Oct 15, there will be a workshop jointly sponsored by CCS and the International Society for Advancement of Cytometry (ISAC) focused on cancer stem cells.
Nodular lymphocyte predominant Hodgkin lymphoma (NLPHL) is a distinct subtype of Hodgkin lymphoma in which T-cell subsets have not been studied specifically. We reviewed 24 cases of NLPHL and compared flow cytometric results with those of 13 progressively transformed germinal centers (PTGC) cases, 78 nonspecific reactive hyperplasia (RH) cases, and 31 classical Hodgkin lymphoma (CHL) cases. A double-positive (CD4+CD8+) T-cell population was present in 58% of NLPHL cases, constituting 10% to 38% of T cells. The cells were CD3+, CD5+, CD2+, CD7+, CD1a– and terminal deoxynucleotidyl transferase–. Similar CD4+CD8+ T cells were identified in 38% of PTGC cases (P = .31), 4% of RH specimens (P < .00001), and 6% of CHL specimens (P < .0001). The presence of a CD4+CD8+ T-cell population in NLPHL may reflect an activated or reactive T-cell subset and should not lead to a misdiagnosis of T-cell lymphoma. This population may be a clue to the diagnosis of NLPHL, particularly in cases with limited tissue.
Mixed lymphohematopoietic chimerism can be induced in mice with bone marrow transplantation (BMT) after a nonmyeloablative preparative regimen that includes cyclophosphamide, anti-T-cell antibody therapy, and thymic i rradiation.These mixed chimeras are resistant to the induction of graft-versus-host disease (GVHD) after delayed donor leukocyte infusions (DLIs), despite a potent lymphohematopoietic graft-versus-host reaction that convert s the mixed chimeric state to a full donor one.Based on this animal model, we initiated a trial of nonmyeloablative therapy with HLA-matched or -mismatched donor BMT and DLI for re f r a c t o ry hematologic malignancies.Tw e n t yone of 36 patients enrolled in this trial received a genotypically (n = 20) or phenotypically (n = 1) HLA-matched donor transplant; results re p o rted here are for those patients only.Preparative therapy consisted of cyclophosphamide in doses of 150 to 200 mg/kg; peritransplant antithymocyte globulin; thymic irradiation (in patients who had not received previous mediastinal radiation therapy); and cyclosporine.Eighteen of 20 evaluable patients developed persistent mixed lymphohematopoietic chimerism as defined by >1% donor peripheral white blood cells until at least day 35 posttransplantation.Ten patients received prophylactic DLI beginning 5 to 6 weeks after BMT for conversion of mixed chimerism to full donor hematopoiesis and to optimize a graft-versus-leukemia effect.Fourteen of 20 evaluable patients (70%) achieved an antitumor response; 8 of these responses were complete, and 6 were p a rtial.Of the 8 evaluable patients who received prophylactic DLI, 6 showed conversion to full donor chimerism.Five of the 9 evaluable patients (56%) who received prophylactic DLI achieved a complete response, compared with 3 of 11 patients (27%) who did not receive prophylactic DLI.Currently 11 patients are alive, and 7 of these are fre e of disease pro g ression at a median follow-up time of 445 days (range, 105-548 days) posttransplantation.Tr a n s p l a nt a t i o n -related complications included cyclophosphamide-induced cardiac toxicity in 3 of 21 patients (14%) and grade II or greater GVHD in 6 patients (29%).One patient (5%) died from a complication of BMT, and 1 patient (5%) died from GVHD after 2 prophylactic DLIs were given for conversion of chimerism.In summary, mixed lymp h ohematopoietic chimerism was re p roducibly induced after a novel nonmyeloablative preparative regimen incorporating chemotherapy, peritransplant antithymocyte globulin, and thymic irradiation, allowing for early administration of DLI in 10 of 21 patients.After treatment, striking antitumor responses were observed in the majority of patients with chemotherapy-re f r a c t o ry hematologic malignancies.
Hodgkin lymphomas are characterised by the presence of rare malignant cells in a background of non-neoplastic inflammatory cells. Flow cytometric analysis of involved tissues is generally not thought to be useful in establishing the diagnosis, because of the small number of neoplastic cells present. However, two recent studies describing a CD4+CD8+ (double-positive) T-cell population in nodular lymphocyte predominant Hodgkin lymphoma (NLPHL) suggest that flow cytometry could play a role in the diagnosis of this Hodgkin lymphoma subtype. In addition, awareness of this unusual T-cell population is important in avoiding a misdiagnosis of a T-cell neoplasm. Although the function of CD4+CD8+ T-cells in NLPHL is not known, studies of phenotypically similar cells in other settings point to a reactive or regulatory role. CD4+CD8+ T-cells have also been identified in the benign entity progressive transformation of germinal centres (PTGC), suggesting a possible relationship between NLPHL and PTGC.
Abstract Conditional deletion of β-catenin in the Müllerian duct mesenchyme results in a degenerative uterus characterized by replacement of the myometrial smooth muscle with adipose tissue. We hypothesized that the mouse myometrium houses somatic smooth muscle progenitor cells that are hormonally responsive and necessary for remodeling and regeneration during estrous cycling and pregnancy. We surmise that the phenotype observed in β-catenin conditionally deleted mice is the result of dysregulation of these progenitor cells. The objective of this study was to identify the mouse myometrial smooth muscle progenitor cell and its niche, define the surface marker phenotype, and show a functional response of these cells to normal myometrial cycling. Uteri were labeled with 5-bromo-2′-deoxyuridine (BrdU) and chased for up to 14 weeks. Myometrial label-retaining cells (LRCs) were observed in the myometrium and stroma throughout the chase period. After 12 weeks, phenotypic analysis of the LRCs by immunofluorescence demonstrated that the majority of LRCs colocalized with α-smooth muscle actin, estrogen receptor-α, and β-catenin. Flow cytometry of myometrial cells identified a myometrial Hoechst 33342 effluxing “side population” that expresses MISRII-Cre-driven YFP. Functional response of LRCs was investigated by human chorionic gonadotropin stimulation of week 12 chase mice and demonstrated sequential proliferation of LRCs in the endometrial stroma, followed by the myometrium. These results suggest that conventional myometrial regeneration and repair is executed by hormonally responsive stem or progenitor cells derived from the Müllerian duct mesenchyme. Disclosure of potential conflicts of interest is found at the end of this article.
