T(1;7) in Acute Myeloblastic Leukemia following Myelodysplastic Syndrome (RAEB-T)

1988 ◽  
Vol 74 (5) ◽  
pp. 555-558 ◽  
Author(s):  
Raffaella Defferrari ◽  
Mario Sessarego ◽  
Gino Santini ◽  
Franco Ajmar
Keyword(s):  
Bone Marrow ◽  
Myelodysplastic Syndrome ◽  
Bone Marrow Cells ◽  
Acute Myeloblastic Leukemia ◽  
Chromosome 7 ◽  
Chromosome 1 ◽  
Refractory Anemia ◽  
Unbalanced Translocation ◽  
Marrow Cells

A case is described of myelodysplastic syndrome (MDS) refractory anemia type with an excess of blasts in transformation with early leukemic evolution (AML-M1). All bone marrow cells examined showed an unbalanced translocation t(1;7). The karyotype was 45, xy, –21, –7, + der dic t(1;7) (q12;q21). There are reports in the literature of the translocation t(l;7) (pll;pll), which leads to trisomy of the long arms of chromosome # 1 and monosomy of the long arms of chromosome # 7. In the case here described the breakpoints of the chromosomes involved in the translocation differ from the classic ones: in this case there is trisomy of the region 1q12→1qter and monosomy of the region 7q21→7qter. Some clinical and cytogenetic considerations are suggested.

Erythropoietin-dependent transformation of myelodysplastic syndrome to acute monoblastic leukemia

Blood ◽  
2001 ◽  
Vol 98 (12) ◽  
pp. 3492-3494 ◽  
Author(s):  
Udomsak Bunworasate ◽  
Hilal Arnouk ◽  
Hans Minderman ◽  
Kieran L. O'Loughlin ◽  
Sheila N. J. Sait ◽  
...  
Keyword(s):  
Myelodysplastic Syndrome ◽  
Bone Marrow Cells ◽  
Tritiated Thymidine ◽  
Flow Cytometric Analysis ◽  
Refractory Anemia ◽  
Laboratory Findings ◽  
Flow Cytometric ◽  
Acute Monoblastic Leukemia ◽  
Leukemia Cutis ◽  
Marrow Cells

Abstract Acute monoblastic leukemia (acute myeloid leukemia [AML], French-American-British type M5a) with leukemia cutis developed in a patient 6 weeks after the initiation of erythropoietin (EPO) therapy for refractory anemia with ringed sideroblasts. AML disappeared from both marrow and skin after the discontinuation of EPO. Multiparameter flow cytometric analysis of bone marrow cells demonstrated coexpression of the EPO receptor with CD45 and CD13 on the surface of blasts. The incubation of marrow cells with EPO, compared to without, resulted in 1.3- and 1.6-fold increases, respectively, in tritiated thymidine incorporation and bromodeoxyuridine incorporation into CD13+ cells. Clinical and laboratory findings were consistent with the EPO-dependent transformation of myelodysplastic syndrome (MDS) to AML. It is concluded that leukemic transformation in patients with MDS treated with EPO may be EPO-dependent and that management should consist of the discontinuation of EPO followed by observation, if clinically feasible.

NKG2D-Mediated Marrow Injury in Paroxysmal Nocturnal Hemoglobinuria and Its Related Disorders.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 3674-3674
Author(s):  
Nobuyoshi Hanaoka ◽  
Tatsuya Kawaguchi ◽  
Kentaro Horikawa ◽  
Shoichi Nagakura ◽  
Sonoko Ishihara ◽  
...  
Keyword(s):  
Bone Marrow ◽  
T Cells ◽  
Paroxysmal Nocturnal Hemoglobinuria ◽  
Bone Marrow Cells ◽  
Close Association ◽  
Bone Marrow Failure ◽  
Γδ T Cells ◽  
Refractory Anemia ◽  
Nkg2d Ligands ◽  
Marrow Cells

Abstract Immune mechanism is considered to exert in the pathogenesis of marrow failure in paroxysmal nocturnal hemoglobinuria (PNH), idiopathic aplastic anemia (AA) and myelodysplastic syndromes (MDS); however, the molecular events are unknown. We have currently reported the appearance of NKG2D ligands such as cytomegalovirus glycoprotein UL16 binding proteins (ULBPs) and MHC class I-related chains A and B (MICA/B) on granulocytes and CD34+ marrow cells of some patients with PNH and its related diseases (Hanaoka N, et al. Blood. 2006;107:1184–1191). ULBP and MICA/B are stress-inducible membrane proteins that appear in infection and transformation. The ligands share NKG2D receptor on lymphocytes such as NK, CD8+ T, and γδ T-cells and promote activation of the lymphocytes. Cells expressing the ligands are then deadly injured by NKG2D+ lymphocytes (Groh, PNAS 1996; Cosman, Immunity 2001). Indeed, cells expressing NKG2D ligands were killed in vitro by autologous NKG2D+ lymphocytes of our patients (Hanaoka N, et al. Blood. 2005;106:304a; Blood. 2006;108:295a). In further analysis, ligands were detected on granulocytes in 47 (53%) of 88 patients: 11 (58%) of 19 PNH, 28 (60%) of 47 AA, and 8 (36%) of 22 refractory anemia. Ligands were also detected on immature bone marrow cells in all 11 patients (3 PNH, 5 AA, and 3 refractory anemia) who permitted analysis of their marrow cells. In the patients, it is conceivable that blood cells were exposed to a certain stress to induce NKG2D ligands, leading to NKG2D-mediated marrow injury. We also observed a close association of the ligand expression with pancytopenia and favorable response to immunosuppressive therapy by prospective analysis of 5 patients (3 AA-PNH syndrome and 2 AA) for more than one year up to 5 years. Thus, we here propose that NKG2D-mediated immunity, which drives both NK and T-cells, is critically implicated in the pathogenesis of bone marrow failure of PNH and its related disorders.

Expression of dlk1 in the Bone Marrow Cells of Patients with Myelodysplastic Syndrome and Its Clinical Significance

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 5042-5042
Author(s):  
Zonghong Shao ◽  
Lanzhu Yue ◽  
Rong Fu ◽  
Lijuan Li ◽  
Erbao Ruan ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Early Diagnosis ◽  
Myelodysplastic Syndrome ◽  
Bone Marrow Cells ◽  
Conflicts Of Interest ◽  
Rt Pcr ◽  
Normal Controls ◽  
Lower Expression ◽  
Bone Marrow Blasts ◽  
Marrow Cells

Abstract Abstract 5042 Objective To investigate the expression of dlk1 gene (delta-like 1) in the bone marrow cells of patients with Myelodysplastic syndrome (MDS), and explore the molecular marker for early diagnosis of MDS. Methods The expression of dlk1 mRNA in the bone marrow cells of cases with MDS, AML and normal controls were measured by RT-PCR, aiming to search for the cytogenetic marker of MDS malignant clone. Results The expression of dlk1 mRNA in bone marrow cells of MDS patients (0.7342±0.3652) was significantly higher than that of normal controls (0.4801±0.1759) (P<0.05), and was significantly positively correlated with the proportion of bone marrow blasts(r=0.467,P<0.05). The expression of dlk1 mRNA significantly increased as the subtype of MDS advanced (P<0.05). Patients with abnormal karyotypes displayed significantly higher expression of dlk1 mRNA (0.9007±0.4334) than those with normal karyotypes (0.6411±0.2630) (P<0.05). Patients with higher expression of dlk1(≥0.8) presented significantly higher malignant clone burden (0.4134±0.3999) than those with lower expression (<0.8) of dlk1 (0.1517±0.3109) (P<0.05). Conclusion dlk1 gene was highly expressed in MDS patients, which increased as the subtype of MDS advanced. The expression of dlk1 mRNA was significantly positively correlated with the proportion of bone marrow blasts. High expression of dlk1 gene suggests high malignant clone burden of MDS. Disclosures: No relevant conflicts of interest to declare.

Immune signatures of bone marrow cells can independently predict prognosis in patients with myelodysplastic syndrome

2021 ◽  
Author(s):  
Yu‐Hung Wang ◽  
Chien‐Chin Lin ◽  
Chi‐Yuan Yao ◽  
Chia‐Lang Hsu ◽  
Cheng‐Hong Tsai ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Myelodysplastic Syndrome ◽  
Bone Marrow Cells ◽  
Immune Signatures ◽  
Marrow Cells

DNA Repair and Longevity: A Possible Link in the Mouse Hematopoietic System.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 1272-1272
Author(s):  
Jeff L. Yates ◽  
Hartmut Geiger ◽  
Gary Van Zant
Keyword(s):  
Bone Marrow ◽  
Dna Damage ◽  
Dna Synthesis ◽  
Dna Damage Response ◽  
Bone Marrow Cells ◽  
S Phase ◽  
Chromosome 7 ◽  
Brdu Incorporation ◽  
Damage Response ◽  
Marrow Cells

Abstract DNA repair efficiency has been postulated to play a role in aging-associated phenotypes as well as in the generation of a variety of cancers. This is especially pertinent in highly proliferative tissues such as the lymphohematopoietic system, since the stem and progenitor compartments are responsible for maintaining proliferative demands within a restricted range for the lifetime of an individual. Hydroxyurea (HU) is a chemotherapeutic drug that targets DNA synthesis by inhibiting the synthesis of the nucleotide substrate resulting in stalled replication forks and single- and double-stranded breaks (DSBs) in the DNA. Recently, our lab has mapped a locus on mouse chromosome 7 that is involved in both organismal lifespan determination and HU sensitivity of bone marrow stem and progenitor cells in the HU-sensitive (25.9% killing), short-lived (540 days) DBA/2J (D2) and HU-insensitive (11.8% killing), long-lived (816 days) C57Bl/6J (B6) strains of mouse. To confirm that this locus is responsible for hydroxyurea sensitivity we generated congenic mice where the locus-containing interval was moved from B6 to D2 (D2. B6 chr. 7) and vice versa (B6. D2 chr. 7). When these animals were treated with HU it was found that the D2 locus imparts a high killing phenotype (38.0%) and the B6 locus confers a low killing phenotype (−4.2%). Using a flow cytometry-based in vivo Bromodeoxyuridine (BrdU) incorporation assay, we measured the recovery of DNA synthesis in the bone marrow in D2 and B6 mice after IP injection of HU (2mg/g). We first determined that DNA synthesis was completely inhibited within 15 minutes of injection and persisted for at least 3 hours in both mouse strains. At 4 hours, bone marrow cells of both strains began to incorporate BrdU, with B6 recovery more rapid than D2, 2.9+/−.5 vs. 7.9+/−3.9 percent BrdU positive cells (p=.01), respectively. Because HU has been used in the past to synchronize cells in G0/G1 and to measure cells in S phase, it was expected that BrdU incorporation would re-initiate within the G0/G1 compartment of cells. Indeed, bone marrow cells from D2 mice incorporated BrdU exclusively within the G0/G1 population. Surprisingly it was found that cells from B6 mice that had an S phase content of DNA prior to HU survived the insult and began to synthesize DNA. It was concluded that B6 bone marrow might have a more robust DNA damage response than that of D2. To study the DNA damage response in the bone marrow we treated mice with HU followed by BrdU and stained the bone marrow cells with an anti-BrdU antibody and an antibody to gamma-H2AX (gH2AX), a histone variant that becomes phosphorylated in the vicinity of DNA DSBs. In both D2 and B6 bone marrow cells it was shown that maximal gH2AX phosphorylation occurred within 1 hour and only occurred in the BrdU+ fraction of the bone marrow cells. Thus it can be concluded that HU causes DNA damage and these two strains of mouse differ in their response due in part to a locus on chromosome 7. Current studies are aimed at identifying the gene(s) of interest in the congenic interval, which include Tfpt and Prkcc.

Alpha-Catenin, ARHGAP21 and β-Catenin Are Abnormally Expressed in Bone Marrow Cells From Patients with Myelodysplatic Syndromes and Are a Possible Target for Decitabine Treatment.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 1778-1778
Author(s):  
Karin Spat Barcellos ◽  
Sheila Maria Winnischofer ◽  
Mariana Lazarini ◽  
Adriana Silva Santos Duarte ◽  
Carolina Louzao Bigarella ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Cell Membrane ◽  
Myelodysplastic Syndrome ◽  
Stromal Cells ◽  
Bone Marrow Cells ◽  
Hematopoietic Cells ◽  
Refractory Anemia ◽  
Beta Catenin ◽  
Healthy Donors ◽  
Cd34 Cells

Abstract Abstract 1778 Poster Board I-804 Introduction Myelodysplastic syndrome (MDS) encloses a group of clonal hematopoietic disorders clinically and morphologically characterized by ineffective hematopoiesis. The gene encoding alpha-catenin (CTNNA1) is expressed at a much lower level in leukemia-initiating stem cells from individuals with MDS del(5q). Thus, loss of alpha-catenin tumor suppressor expression in hematopoietic cells may provide a growth advantage that collaborates MDS pathogenesis. ARHGAP21, a negative regulator of RhoGTPase signaling pathways, is a partner of alpha-catenin that controls its recruitment to the adherens junctions. ARHGAP21 is upregulated during myeloid differentiation, and could be involved in the malignant process of hematopoietic cells. In addition, alpha-catenin is a target for decitabine (DAC) treatment, a demethylating agent with potent antitumorigenic properties against MDS. The aim of this work was to evaluate the expression of alpha-catenin, ARHGAP21 and beta-catenin (gene CTNNB1) in bone marrow cells from MDS patients with or without del(5q) and to analyze CTNNA1, ARHGAP21 and CTNNB1 expression after DAC treatment. PATIENTS AND METHODS cells were isolated from bone marrow of 6 MDS patients, including 5 refractory anemia (RA), being two with del(5q), and 1 refractory anemia with excess blasts (RAEB), based on the French-American-British classification, and 4 control subjects (normal hematopoietic tissues were obtained from healthy donors). The study was approved by the National Ethical Committee Board and bone marrow samples were collected at the Hematology and Hemotherapy Center, University of Campinas, after all participants provided informed written consent. Alpha-catenin, ARHGAP21 and beta-catenin localization in CD34+ cells was obtained using confocal microscopic analysis. ARHGAP21 localization was also analyzed in HS-5 stromal cells that were submitted to a CTNNA1 RNA interference (RNAi) approach. Leukemia cells lines (HL-60 and P-39) and bone marrow mononuclear cells obtained from 7 MDS patients, 5 RA and 2 refractory anemia with ringed sideroblasts (RARS), were treated with DAC for 72 hours; then mRNA expression of CTNNA1, ARHGAP21 and CTNNB1 was analyzed by Real-time PCR (normalized by GAPDH and beta-actin). RESULTS alpha-catenin, ARHGAP21 and beta-catenin are preferentially localized in the nucleus of CD34+ cells from MDS patients in contrast to the preferential cytoplasm and membrane localization in healthy donors and in MDS patients with del(5q). In del(5q) patients and healthy donors, ARHGAP21 and alpha-catenin co-localizated in the cell membrane. ARHGAP21 was abnormally expressed in cells with decreased CTNNA1 expression: in HS-5 stromal cells, ARHGAP21 was localized at the cytoplasm (mainly in the perinuclear region) and at the nucleus, in contrast, ARHGAP21 was poorly detectable in the nucleus of CTNNA1-RNAi treated cells. DAC treatment of MDS cells and leukemia cell lines induced CTNNA1, ARHGAP21, and CTNNB1 expression in a dose-dependent way. In HL60 and P39 cells, ARHGAP21 relocate to the cell membrane after DAC treatment. CONCLUSION The abnormal localization of alpha-catenin, ARHGAP21 and beta-catenin in MDS may compromise the reorganization of actin dynamics at sites of cell–cell contact that stabilizes cadherin-mediated cell–cell adhesion; moreover, these results also suggest a deficient recruitment of alpha-catenin to the cell membrane and an aberrant signaling in the Wnt pathway. In addition, ARHGAP21, alpha-catenin and beta-catenin are a target for DAC treatment in MDS. Supported by: FAPESP. Keywords: alpha-catenin, ARHGAP21, beta-catenin, myelodysplastic syndrome, Rho-GAP, decitabine Disclosures No relevant conflicts of interest to declare.

scholarly journals Distinctive microRNA expression profiles in CD34+ bone marrow cells from patients with myelodysplastic syndrome

2010 ◽  
Vol 19 (3) ◽  
pp. 313-319 ◽  
Author(s):  
Michaela Dostalova Merkerova ◽  
Zdenek Krejcik ◽  
Hana Votavova ◽  
Monika Belickova ◽  
Alzbeta Vasikova ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Myelodysplastic Syndrome ◽  
Bone Marrow Cells ◽  
Expression Profiles ◽  
Microrna Expression ◽  
Marrow Cells
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