Journal of hematotherapy & stem cell research最新文献

{"title":"Establishment of mouse embryonic fibroblast cell lines that promote ex vivo expansion of human cord blood CD34+ hematopoietic progenitors.","authors":"Huiying Qiu,&nbsp;Yoshihiro Fujimori,&nbsp;Shunro Kai,&nbsp;Yuka Fujibayashi,&nbsp;Keisuke Nishioka,&nbsp;Hiroshi Hara","doi":"10.1089/152581603321210127","DOIUrl":"https://doi.org/10.1089/152581603321210127","url":null,"abstract":"<p><p>The development of culture systems that facilitate ex vivo maintenance and expansion of transplantable hematopoietic progenitor cells (HPC) is vital to stem cell transplantation. The use of a monolayer of stromal cells on which to grow HPC in direct contact allows high efficiency ex vivo expansion of HPC. Here, we report an establishment of three murine embryonic fibroblast stromal cell lines from adherent cells of day-12 mouse embryos. Among them, HYMEQ-5 was most efficient in supporting long-term maintenance of human umbilical cord blood (CB) CD34(+) cells. Human CB CD34(+) cells cultured on HYMEQ-5 in the presence of stem cell factor (SCF), thrombopoietin, and flk-ligand (FL) showed high expansion of CD34(+)CD38(-) cells and highly proliferative potential-colony forming cells (HPP-CFC). Direct cell-to-cell contact between CD34(+) cells and HYMEQ-5 was important for this expansion. RT-PCR analysis showed that HYMEQ-5 produced FL, SCF, interleukin-6, and macrophage colony-stimulating factor (M-CSF). Expanded CB CD34(+) cells efficiently reconstituted hematopoiesis in nonobese diabetic/severe combined immunodeficient disease (NOD/SCID) mice. These findings suggest that HYMEQ-5 provides a milieu that supports long-term human hematopoiesis as well as ex vivo expansion of human CB CD34(+) HPC. This cell line may facilitate elucidation of the mechanism of cellular interactions between HPC and stromal cells.</p>","PeriodicalId":80030,"journal":{"name":"Journal of hematotherapy & stem cell research","volume":"12 1","pages":"39-46"},"PeriodicalIF":0.0,"publicationDate":"2003-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1089/152581603321210127","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"22312492","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Fetal human hematopoietic stem cells can differentiate sequentially into neural stem cells and then astrocytes in vitro.","authors":"Hsiao-Nan Hao,&nbsp;Jane Zhao,&nbsp;Ronald L Thomas,&nbsp;Graham C Parker,&nbsp;William D Lyman","doi":"10.1089/152581603321210109","DOIUrl":"https://doi.org/10.1089/152581603321210109","url":null,"abstract":"<p><p>In some rodent models, there is evidence that hematopoietic stem cells (HSC) can differentiate into neural cells. However, it is not known whether humans share this potential, and, if so, what conditions are sufficient for this transdifferentiation to occur. We addressed this question by assessing the ability of fetal human liver CD34(+)/CD133(+)/CD3(-) hematopoietic stem cells to generate neural cells and astrocytes in culture. We cultured fetal liver-derived hematopoietic stem cells in human astrocyte culture-conditioned medium or using a method wherein growing human astrocytes were separated from cultured, nonadherent hematopoietic stem cells by a semipermeable membrane in a double-chamber co-culture system. Hematopoietic stem cell cultures were probed for neural progenitor cell marker expression (nestin and bone morphogenic protein-2 [BMP-2]) during growth in both culture conditions. RT-PCR, western blotting, and immunocytochemistry assays showed that cells cultured in either condition expressed nestin mRNA and protein and BMP-2 mRNA. HSC similarly cultured in nonconditioned medium or in the absence of astrocytes did not express either marker. Cells expressing these neural markers were transferred and cultured on poly-D-lysine-coated dishes with nonconditioned growth medium for further study. Immunocytochemistry demonstrated that these cells differentiated into astrocytes after 8 days in culture as indicated by their morphology and expression of the astrocytic markers glial fibrillary acidic protein (GFAP) and S100, as well as by their rate of proliferation, which was identical to that of freshly isolated fetal brain astrocytes. These findings demonstrate that neural precursor gene expression can be induced when human hematopoietic stem cells are exposed to a suitable microenvironment. Furthermore, the neural stem cells generated in this environment can then differentiate into astrocytes. Therefore, human hematopoietic stem cells may be an alternative resource for generation of neural stem cells for therapy of central nervous system defects resulting from disease or trauma.</p>","PeriodicalId":80030,"journal":{"name":"Journal of hematotherapy & stem cell research","volume":"12 1","pages":"23-32"},"PeriodicalIF":0.0,"publicationDate":"2003-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1089/152581603321210109","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"22312490","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Autologous blood cell transplantation in multiple myeloma: impact of CD34+ cell selection with long follow-up.","authors":"K Remes,&nbsp;M Itälä,&nbsp;M Kauppila,&nbsp;T-T Pelliniemi,&nbsp;A Rajamäki","doi":"10.1089/152581603321210145","DOIUrl":"https://doi.org/10.1089/152581603321210145","url":null,"abstract":"<p><p>Positive CD34(+) selection to purge blood cell harvests is one way to attempt to reduce the high relapse risk after high-dose chemotherapy (HDT) supported by autologous blood cell transplantation (ABCT) in patients with multiple myeloma (MM). Until recently, however, the impact of CD34(+) selection, if any, on long-term clinical outcome in MM has remained obscure. We have analyzed engraftment kinetics, response to HDT, progression-free survival (PFS), and overall survival (OS) for 64 consecutive MM patients who have been treated with up-front HDT plus ABCT at our institution between 1993 and 1998. Nonrandomized comparisons were made between transplants with unselected (39 patients) and CD34(+)-selected (25 patients) grafts. The engraftment kinetics, need of blood product support, discharge time from hospital, and response to HDT were similar for both unselected and selected transplants. The median PFS was also similar (26 and 30 months, respectively) for the both groups. With a median follow-up time for the survivors of 67.5 months, the median OS (78 and 75 months, respectively) did not differ between transplants with unselected and selected grafts. In conclusion, this nonrandomized study suggests that positive CD34(+) selection has no beneficial impact on long-term outcome of patients with MM.</p>","PeriodicalId":80030,"journal":{"name":"Journal of hematotherapy & stem cell research","volume":"12 1","pages":"63-70"},"PeriodicalIF":0.0,"publicationDate":"2003-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1089/152581603321210145","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"22311982","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Rapid, large-scale generation of highly pure cytomegalovirus-specific cytotoxic T cells for adoptive immunotherapy.","authors":"Aaron E Foster,&nbsp;David J Gottlieb,&nbsp;Marina Marangolo,&nbsp;Anna Bartlett,&nbsp;Yi-Chiao Li,&nbsp;Geoffrey W Barton,&nbsp;Jose A Romagnoli,&nbsp;Kenneth F Bradstock","doi":"10.1089/152581603321210172","DOIUrl":"https://doi.org/10.1089/152581603321210172","url":null,"abstract":"<p><p>Adoptive transfer of donor-derived cytomegalovirus (CMV)-specific cytotoxic T cell (CTL) clones can restore immunity in allogeneic stem cell transplant recipients, providing protection against CMV disease. Current methods for selecting and expanding CMV-specific T cell clones are technically difficult, making adoptive T cell therapy impractical for routine clinical use. In this study, we describe a method for ex vivo generation and expansion of high-purity CMV-specific CTL using peptide-pulsed dendritic cells as antigen-presenting cells. Generation of CMV-specific CTL in numbers sufficient for clinical use in the time span of 4 weeks was accomplished in 6 of 8 CMV-seropositive donors. Examination of pp65 specificity by HLA/peptide tetramer staining demonstrated that a purity of greater than 95% peptide-specific cells could be obtained after two weekly stimulations and retained after further expansion for 3-4 weeks. Median expansion of total cell number was greater than 500-fold and expansion of peptide-specific CTL by tetramer staining was greater than 1.7 x 10(5)-fold. Four weeks after initiating CTL culture, we were able to generate greater than 10(9) total cells that specifically lysed target cells loaded with CMV peptide and cells infected with CMV. This simple and rapid method for generating high-purity CMV-specific CTL for adoptive immunotherapy is currently being examined for routine clinical use for allogeneic stem cell transplantation.</p>","PeriodicalId":80030,"journal":{"name":"Journal of hematotherapy & stem cell research","volume":"12 1","pages":"93-105"},"PeriodicalIF":0.0,"publicationDate":"2003-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1089/152581603321210172","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"22311985","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Src kinase, but not the src kinase family member p56lck, mediates stromal cell-derived factor 1alpha/CXCL12-induced chemotaxis of a T cell line.","authors":"Seiichi Okabe,&nbsp;Seiji Fukuda,&nbsp;Hal E Broxmeyer","doi":"10.1089/152581602321080583","DOIUrl":"https://doi.org/10.1089/152581602321080583","url":null,"abstract":"Stromal cell-derived factor 1 (SDF-1/CXCL12) is believed to mediate migration of leukocytes. To explore potential mechanisms, we evaluated the signal transduction pathways activated by SDF-1 in the Jurkat T cell line. Src kinase was phosphorylated and mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) activated in a time-related fashion after SDF-1 stimulation. Chemotaxis of Jurkat cells was partially blocked by pretreatment with the src kinase inhibitor PP2 in a dose-dependent manner. Wiskott-Aldrich Syndrome Protein (WASP) regulates actin polymerization and cytoskeletal organization in T cells. We found WASP complexed to activated src after SDF-1 stimulation, suggesting a possible interacting role for src kinase and WASP in mediating SDF-1 action. J.CaM1.6 cells, which have lost expression of the src kinase p56(lck) (lck), responded to chemotaxis induced by SDF-1 as well as the parental Jurkat cells. Because J.CaM1.6 cells respond as well as the parental cells to SDF-1 in terms of ERK activation and tyrosine phosphorylation of WASP after SDF-1 stimulation, it appears that src kinase, but not the src kinase family member lck, mediates chemotaxis of Jurkat cells in response to SDF-1 induction and that src kinase may link with WASP in this effect.","PeriodicalId":80030,"journal":{"name":"Journal of hematotherapy & stem cell research","volume":"11 6","pages":"923-8"},"PeriodicalIF":0.0,"publicationDate":"2002-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1089/152581602321080583","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"22249610","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hematopoietic reconstitution of irradiated, stem cell-injected mice: early dynamics of restoration of the cell lineages of the spleen and bone marrow.","authors":"Sandra C Miller","doi":"10.1089/152581602321080628","DOIUrl":"https://doi.org/10.1089/152581602321080628","url":null,"abstract":"<p><p>Hematopoietic stem cells, numbering approximately 1/100,000 cells in mammalian bone marrow, are capable of complete hematopoietic and immune reconstitution upon injection into a myeloablated host. The present study aimed to analyze the earliest events in reconstitution of lethally irradiated, host murine bone marrow and spleen, after injecting purified Thy 1(lo)Lin(-)Sca-1(+) stem cells. Thy-1(lo)Lin(-)Sca-1(+) cells were isolated by fluorescence-activated cell sorting (FACS) from the bone marrow of 4-week-old C57BL(Thy1.1, Ly5.1) mice and injected into preirradiated, syngeneic hosts. These stem cells were also injected into congenic hosts, i.e., C57BL(Thy1.2, Ly5.2), and confirmed the donor origin of hematopoietic cells in the reconstituted host mice. Hematologically stained smears of the spleen and bone marrow of stem cell-injected recipients were prepared at 11, 14, 17, 21, 24, and 28 days after stem cell injection, and nucleated erythroid cells, mature granulocytes, and their myeloid precursors, monocytes, and large and small lymphocytes were recorded as a proportion of all nucleated cells in each organ at each time interval. The results indicated that in the earliest post stem cell injection intervals, both organs were predominantly erythroid and myeloid. Only at the later intervals did both organs show high proportions of large lymphoid cells and their progeny, small lymphocytes. Thus, early (<1 month) dynamics of hematopoietic reconstitution after transplantation of purified hematopoietic stem cells, is cell lineage specific.</p>","PeriodicalId":80030,"journal":{"name":"Journal of hematotherapy & stem cell research","volume":"11 6","pages":"965-70"},"PeriodicalIF":0.0,"publicationDate":"2002-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1089/152581602321080628","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"22249614","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Early apoptosis largely accounts for functional impairment of CD34+ cells in frozen-thawed stem cell grafts.","authors":"Fransien de Boer,&nbsp;Angelika M Dräger,&nbsp;Herbert M Pinedo,&nbsp;Floortje L Kessler,&nbsp;M Monnee-van Muijen,&nbsp;Geert Weijers,&nbsp;Guus Westra,&nbsp;Elsken van der Wall,&nbsp;Tanja Netelenbos,&nbsp;Jan W Oberink,&nbsp;Peter C Huijgens,&nbsp;Gerrit J Schuurhuis","doi":"10.1089/152581602321080619","DOIUrl":"https://doi.org/10.1089/152581602321080619","url":null,"abstract":"<p><p>Quality assessment of stem cell grafts is usually performed by flow cytometric CD34(+) enumeration or assessment of clonogenic output of fresh material. Previously, we identified the occurrence of early apoptosis, not detectable with the permeability marker 7-amino actinomycin D (7-AAD), in purified frozen-thawed CD34(+) cells, using the vital stain Syto16. Syto(high)/7-AAD(-) cells were defined as viable, Syto16(low)/7-AAD(-) cells as early apoptotic and Syto16(low)/7-AAD(+) as dead. This was confirmed in a subsequent study using frozen-thawed transplants of lymphoma patients. In the present study on grafts from multiple myeloma and lymphoma patients, we investigated the functional consequences of the early apoptotic process. The mean Syto16-defined viability was 41 and 42%, respectively, for both graft groups, compared to 78% and 72%, respectively, using 7-AAD only. The established early apoptosis marker annexin V missed roughly 50% of the early apoptosis detected with Syto16. In contrast, viability of CD34(+) cells in nonmanipulated whole blood transplants from a matched group of lymphoma patients, after 72 h of storage at 4 degrees C, was more than 90%, even with the Syto16 assay. CFU recovery (median 26-33%) after cryopreservation matched CD34(+) recovery after Syto16, but not 7-AAD correction. In contrast, colony-forming unit (CFU) recovery in the whole blood transplant was close to 100%. Furthermore, early apoptotic CD34(+) cells had lost migratory ability toward stromal cell derived factor-1alpha (SDF-1alpha). The establishment of a Syto16(high)/7-AAD(-) proportion of CD34(+) cells offers a new approach for a more correct determination of the number of viable nonapoptotic CD34(+) cells in stem cell grafts. Further development of this assay should allow its incorporation into the routine CD34(+) assessment of post-thawed samples in clinical flow cytometry laboratories.</p>","PeriodicalId":80030,"journal":{"name":"Journal of hematotherapy & stem cell research","volume":"11 6","pages":"951-63"},"PeriodicalIF":0.0,"publicationDate":"2002-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1089/152581602321080619","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"22249613","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification of tumor-associated HLA-ligands in the post-genomic era.","authors":"Markus Schirle","doi":"10.1089/152581602321080538","DOIUrl":"https://doi.org/10.1089/152581602321080538","url":null,"abstract":"<p><p>Over 10 years ago, the identification of the first tumor-specific T cell epitope shed light on the molecular principles underlying the phenomenon of tumor eradication by the immune system. Since then, a considerable number of different approaches for this task have been introduced and employed successfully, reflecting the growing knowledge about the cellular processes preceding antigen presentation as well as significant technical developments. This review tries to give an overview over available conventional strategies as well as current developments that utilize the potent large-scale screening tools of the post-genomic era.</p>","PeriodicalId":80030,"journal":{"name":"Journal of hematotherapy & stem cell research","volume":"11 6","pages":"873-81"},"PeriodicalIF":0.0,"publicationDate":"2002-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1089/152581602321080538","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"22249675","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Homing of purified murine lymphohematopoietic stem cells: a cytokine-induced defect.","authors":"Jan Cerny,&nbsp;Mark Dooner,&nbsp;Christina McAuliffe,&nbsp;Houri Habibian,&nbsp;Kimberly Stencil,&nbsp;Virla Berrios,&nbsp;Judy Reilly,&nbsp;Jane Carlson,&nbsp;Anna Maria Cerny,&nbsp;Lionel d'Hondt,&nbsp;Brian Benoit,&nbsp;Jean-Francois Lambert,&nbsp;Gerald Colvin,&nbsp;Susan Nilsson,&nbsp;Pamela Becker,&nbsp;Peter Quesenberry","doi":"10.1089/152581602321080574","DOIUrl":"https://doi.org/10.1089/152581602321080574","url":null,"abstract":"<p><p>This study was designed to establish a direct homing assay using purified lineage-negative Sca-1-positive (Lin(-) Sca(+)) murine bone marrow cells and to evaluate the effects of cytokines on homing. C57BL/6 Lin(-) Sca(+) marrow stem cells were labeled with 5-(and 6)-carboxyfluorescein diacetate succinimidyl ester (CFDA-SE) and then injected by tail vein into untreated C57BL/6 mice. Marrow was harvested at various times after cell infusion and analyzed on a high-speed MoFlo cell sorter for fluorescent positive events, using a large event analysis, with at least 16 million total events analyzed. We have shown that homing of Lin(-) Sca(+) cells plateaus by 1 h, and at 3 h post-infusion is linear between 50,000 and 1,000,000 infused cells. This forms a base for a homing assay in which 250,000 CFDA-SE labeled Lin(-) Sca(+) marrow cells are infused and then recovered from marrow 3 h later, followed by a large-event fluorescence-activated cell sorting (FACS) analysis. We found that 7.45-9.32% of infused cells homed and that homing of stem cells cultured for 48 h in interleukin-3 (IL-3), IL-6, IL-11, and steel factor cultured cells was defective when compared to noncultured cells. Exposure of marrow stem cells to IL-3, IL-6, IL-11, and steel factor induces a stem cell homing defect, which probably underlies the engraftment defect previously characterized under these conditions.</p>","PeriodicalId":80030,"journal":{"name":"Journal of hematotherapy & stem cell research","volume":"11 6","pages":"913-22"},"PeriodicalIF":0.0,"publicationDate":"2002-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1089/152581602321080574","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"22249679","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Acute promyelocytic leukemia M3: cytomorphologic, immunophenotypic, cytogenetic, and molecular variants.","authors":"Mirna Sucić,&nbsp;Renata Zadro,&nbsp;Branka Burazer,&nbsp;Boris Labar,&nbsp;Damir Nemet,&nbsp;Mirando Mrsić,&nbsp;Igor Aurer,&nbsp;Sanja Mrsić,&nbsp;Vlasta Hitrec,&nbsp;Dubravka Boban,&nbsp;Mirjana Marković-Glamocak,&nbsp;Drago Batinić,&nbsp;Branka Uzarević,&nbsp;Ana Stavljenić-Rukavina","doi":"10.1089/152581602321080600","DOIUrl":"https://doi.org/10.1089/152581602321080600","url":null,"abstract":"<p><p>Acute promyelocytic leukemia (APL) M3 is an acute myeloid leukemia (AML) subtype characterized by proliferation of malignant promyelocytes with mature myeloid immunophenotype and the translocation t(15;17)(q22;q11), which results in the fusion of retinoic acid receptor-alpha (RARalpha) gene on chromosome 17 and the gene PML on chromosome 15. There are three M3 morphologic variants: the typical hypergranular form and the microgranular and basophilic variants. Although most leukemic cells in M3 patients express t(15;17), other cytogenetic abnormalities have also been reported. Also, there are three molecular variants of the PML/RARalpha transcript (bcr1, bcr2, bcr3). Blasts had typical hypergranular appearance (13 patients) with a mature myeloid immunophenotype (HLA-DR(-),CD13(+), and/or CD33(+)) (10 patients) in the majority of patients with M3 followed in this study. The typical translocation [t(15;17)(q22;q11)] was detected by cytogenetic analysis in 5 M3 patients, but PML/RARalpha was positive in 13 out of 15 patients, as assessed by RT-PCR (8 patients with bcr1 and 5 with bcr3 subtype). Cytogenetic diversity was found in three patients (1 with t(17;17), 1 with +8, and 1 with add (7)(q22); -7; +8). According to many studies, leukemic cell heterogeneity in APL influences the clinical outcome of disease. The analysis of certain leukemic cell characteristics on the clinical outcome in our study revealed that patients with bcr3 had shorter medians of first remission and survival in comparison to patients with the bcr1 isoform of PML/RARalpha. Also, the clinical relapse of disease in 4 APL patients with reverted PML/RAR alpha positivity is consistent with the view that detection of PML/RARalpha by RT-RCR in patients in remission implies a poor prognosis. On the contrary, lack of detection of PML/RARalpha by RT-PCR at least three times is a sign of long remission and survival.</p>","PeriodicalId":80030,"journal":{"name":"Journal of hematotherapy & stem cell research","volume":"11 6","pages":"941-50"},"PeriodicalIF":0.0,"publicationDate":"2002-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1089/152581602321080600","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"22249612","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}