scholarly journals Cytochemistry of acute promyelocytic leukemia (M3): leukemic promyelocytes exhibit heterogeneous patterns in cellular differentiation

Blood ◽  
1985 ◽  
Vol 66 (2) ◽  
pp. 350-357 ◽  
Author(s):  
M Tomonaga ◽  
Y Yoshida ◽  
M Tagawa ◽  
I Jinnai ◽  
K Kuriyama ◽  
...  
Keyword(s):  
Acute Promyelocytic Leukemia ◽  
Cellular Differentiation ◽  
Remission Rate ◽  
Promyelocytic Leukemia ◽  
Control Group ◽  
Granulocytic Differentiation ◽  
Cytochemical Investigation ◽  
Significant Difference ◽  
Monocytic Lineage

Abstract Cytochemical investigation of leukemic promyelocytes from 25 cases of acute promyelocytic leukemia (M3) disclosed two major cellular differentiation categories: (1) the pure neutrophilic (N) type (16 cases) with strong myeloperoxidase (MPO) and naphthol-ASD chloroacetate esterase (Es-chl), but lacking the monocytic enzyme NaF-sensitive alpha- naphthyl butyrate esterase (Es-b), and (2) the mixed neutrophilic/monocytoid (N/M) type (seven cases) with strong Es-b as well as strong MPO, all cases exhibiting Es-dual (Es-b + Es-chl) positive cells. Two more cases with unusual phenotypes were noted: one with intense lysozyme activity but without Es-b and the other with toluidine blue-methachromasia and negative MPO. Promyelocytes from the control group, consisting of nine cases of t(8;21) M2 AML and ten cases with normal bone marrow, lacked such cytochemical heterogeneity. HL-60, an M3 cell line that can be induced to differentiate toward monocytic lineage in vitro, was almost negative for Es-b in the uninduced condition. Cytogenetically, eight cases of N type and five of N/M type had the t(15;17) abnormality. Thus at least two differentiation patterns were observed in M3 leukemia with fidelity (N type) and infidelity (N/M type) for normal granulocytic differentiation. In this series, there was no statistically significant difference in clinical features (remission rate and survival) between the two types. Our study suggests that the development of M3 leukemia is not exclusively restricted to the neutrophilic pathway, but more heterogeneously related to myelomonocytic differentiation.

scholarly journals Cytochemistry of acute promyelocytic leukemia (M3): leukemic promyelocytes exhibit heterogeneous patterns in cellular differentiation

Blood ◽  
1985 ◽  
Vol 66 (2) ◽  
pp. 350-357
Author(s):  
M Tomonaga ◽  
Y Yoshida ◽  
M Tagawa ◽  
I Jinnai ◽  
K Kuriyama ◽  
...  
Keyword(s):  
Acute Promyelocytic Leukemia ◽  
Cellular Differentiation ◽  
Remission Rate ◽  
Promyelocytic Leukemia ◽  
Control Group ◽  
Granulocytic Differentiation ◽  
Cytochemical Investigation ◽  
Significant Difference ◽  
Monocytic Lineage

Cytochemical investigation of leukemic promyelocytes from 25 cases of acute promyelocytic leukemia (M3) disclosed two major cellular differentiation categories: (1) the pure neutrophilic (N) type (16 cases) with strong myeloperoxidase (MPO) and naphthol-ASD chloroacetate esterase (Es-chl), but lacking the monocytic enzyme NaF-sensitive alpha- naphthyl butyrate esterase (Es-b), and (2) the mixed neutrophilic/monocytoid (N/M) type (seven cases) with strong Es-b as well as strong MPO, all cases exhibiting Es-dual (Es-b + Es-chl) positive cells. Two more cases with unusual phenotypes were noted: one with intense lysozyme activity but without Es-b and the other with toluidine blue-methachromasia and negative MPO. Promyelocytes from the control group, consisting of nine cases of t(8;21) M2 AML and ten cases with normal bone marrow, lacked such cytochemical heterogeneity. HL-60, an M3 cell line that can be induced to differentiate toward monocytic lineage in vitro, was almost negative for Es-b in the uninduced condition. Cytogenetically, eight cases of N type and five of N/M type had the t(15;17) abnormality. Thus at least two differentiation patterns were observed in M3 leukemia with fidelity (N type) and infidelity (N/M type) for normal granulocytic differentiation. In this series, there was no statistically significant difference in clinical features (remission rate and survival) between the two types. Our study suggests that the development of M3 leukemia is not exclusively restricted to the neutrophilic pathway, but more heterogeneously related to myelomonocytic differentiation.

scholarly journals Clinical Study on Prospective Efficacy of All-Trans Acid, Realgar-Indigo Naturalis Formula Combined with Chemotherapy as Maintenance Treatment of Acute Promyelocytic Leukemia

2014 ◽  
Vol 2014 ◽  
pp. 1-7 ◽  
Author(s):  
Li Xiang-Xin ◽  
Wang Lu-Qun ◽  
Li Hao ◽  
He Xiao-Peng ◽  
Li Fang-Lin ◽  
...  
Keyword(s):  
Acute Promyelocytic Leukemia ◽  
Maintenance Treatment ◽  
Adverse Reactions ◽  
Residual Disease ◽  
Standard Dose ◽  
Promyelocytic Leukemia ◽  
Remission Induction ◽  
Control Group ◽  
Significant Difference ◽  
Indigo Naturalis

Objectives. To test the efficiency and safety of sequential application of retinoic acid (ATRA), Realgar-Indigo naturalis formula (RIF) and chemotherapy (CT) were used as the maintenance treatment in patients with acute promyelocytic leukemia (APL).Methods. This was a retrospective study of 98 patients with newly diagnosed APL who accepted two different maintenance treatments. After remission induction and consolidation chemotherapy according to their Sanz scores, patients received two different kinds of maintenance scheme. The first regimen was using ATRA, RIF, and standard dose of CT sequentially (ATRA/RIF/CT regimen), while the second one was using ATRA and low dose of chemotherapy with methotrexate (MTX) plus 6-mercaptopurine (6-MP) alternately (ATRA/CTlowregimen). The OS, DFS, relapse rate, minimal residual disease, and adverse reactions in two groups were monitored and evaluated.Results. ATRA/RIF/CT regimen could effectively reduce the chance of relapse in different risk stratification of patients, but there was no significant difference in 5-year DFS rate and OS rate between the two groups. Besides, the patients in the experimental group suffered less severe adverse reactions than those in the control group.Conclusions. The repeated sequential therapeutic regimen to APL with ATRA, RIF, and chemotherapy is worth popularizing for its high effectiveness and low toxicity.

Vitamin E Succinate Induces Remission and Prolongs Survival in a Syngenic Transplant Model of Acute Promyelocytic Leukemia.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 4953-4953
Author(s):  
Rodrigo S. Abreu e Lima ◽  
Priscila S. Scheucher ◽  
Bárbara A.A. Santana ◽  
Ana Carolina T. Pintão ◽  
Ana Sílvia G. Lima ◽  
...  
Keyword(s):  
Vitamin E ◽  
Acute Promyelocytic Leukemia ◽  
Annexin V ◽  
Promyelocytic Leukemia ◽  
Rank Test ◽  
Histopathological Analysis ◽  
Vitamin E Succinate ◽  
Significant Difference ◽  
Transplant Model

Abstract Vitamin E Succinate (VES) is a semisinthetic analogue of vitamin E with pro-apoptotic activity against several tumor cell lines and it has reported that the association of VES and other antioxidants with first-line chemotherapy may prolong survival of patients with ovarian carcinoma without significant adverse effects. Recently, we have demonstrated in vitro that VES induces apoptosis in primary cells from patients with Acute Promyelocytic Leukemia (APL) as well as in NB4 cells. In order to test in vivo the efficacy of VES treatment, we used a syngenic transplant model of APL. Leukemic blasts from PML/RARα transgenic mice (TM) were IV injected in non transgenic littermates. Recipients were irradiated with 700 cGy 24h prior to transplant. Massive infiltration of bone marrow (BM), spleen and liver was invariable detected by 21st Day. Forty-eight mice were randomly assigned to receive daily intraperitoneal (ip) injections of : VES (50UI/g/d) (n=8), Retinoic Acid (RA) (1.5μg/g/d) (n=7), As2O3 (2.5μg/g/d) (n=8) or the association VES + RA (n=7) and VES + As2O3 (n= 8) at the same doses. Control mice (n=10) were treated with vehicle (DMSO). Treatment was started four days after transplantation and maintained for 21 consecutive days. Survival analysis was based on Kaplan-Meyer estimation and groups were compared by the long-rank test. In any of the five therapeutic arms hematology remission was achieve and survival was significantly longer than in DMSO treated group (P<0.05) (Mean survival time of control: 29.8 days, 95% C.I. = 23.3 – 36.3 days; VES: 66 days, 95%CI = 51.9 – 80.1 days; RA: 60.7 days, 95% CI = 48.1 – 73.2 days; As2O3: 69.7 days, 95% CI = 55.4 –84 days; VES+RA: 49.8 days, 95% CI = 29 – 70.5 days; VES+ As2O3: 70.3 days, 95% CI = 57 – 83.5 days. Treatment toxicity was evaluated by histopathological analysis of heart, lung, brain, liver and kidney paraffin embedded specimens, and no significant organ damage was detected. In order to determine if the antileukemic effect of VES was due to induction of apoptosis, leukemic cells obtained from spleen were treated in vitro with 10, 20, 40μg/mL of VES or DMSO. After 24h cells were harvested and stained with anti-CD117 and anti-annexin V antibody conjugated with phycoerythrin (PE) or fluorescein isothyocyanate (FITC), and the number of CD117 / Annexin V double positive cells (apoptotic) was determined by flow cytometry (FC). The mean percentage of apoptotic cells in samples treated with 40μg/mL of VES (but not with 10 or 20μg/mL) was significantly higher than in controls (83 ± 8% versus 56 ± 4 %, p< 0.05). Differentiation was evaluated morphologically on Leishman stained cytospin preparations after 72h of in vitro treatment of VES at the same doses above. No significant difference in the number of mature granulocytic cells between treated and control samples was observed. In conclusion, our results demonstrate that treatment with VES alone or in combination with RA or As2O3 was well tolerated and extremely effective, and therefore may represent an alternative therapy to relapsed and/or refractory APL cases.

scholarly journals All-transretinoic acid followed by intensive chemotherapy gives a high complete remission rate and may prolong remissions in newly diagnosed acute promyelocytic leukemia: a pilot study on 26 cases

Blood ◽  
1992 ◽  
Vol 80 (9) ◽  
pp. 2176-2181 ◽  
Author(s):  
P Fenaux ◽  
S Castaigne ◽  
H Dombret ◽  
E Archimbaud ◽  
M Duarte ◽  
...  
Keyword(s):  
Pilot Study ◽  
Complete Remission ◽  
Acute Promyelocytic Leukemia ◽  
Remission Rate ◽  
Promyelocytic Leukemia ◽  
Intensive Chemotherapy ◽  
Newly Diagnosed ◽  
Historical Comparison

Abstract We entered 26 patients with newly diagnosed acute promyelocytic leukemia (APL) in a pilot study of all-transretinoic acid (ATRA) followed by intensive chemotherapy. Median age was 46 (range 25 to 63). No patient presented with leukocytes > 10 x 10(9)/L or had the microgranular APL variant. Cytogenetic analysis (25 patients) found a t(15;17) in 24 cases. Patients were scheduled to receive ATRA (45 mg/m2/d) until complete remission, followed by an intensive daunorubicin (DNR) + Ara C course (“4 + 7” course), then three “2 + 5” DNR + Ara C courses and maintenance chemotheapy. However, the “4 + 7” course was administered in emergency if hyperleukocytosis rapidly developed to prevent leukostasis. Twenty-five patients (96%) achieved CR, 14 with ATRA alone and 11 after the addition of the “4 + 7” course on day 2 to 30 of treatment, because leukocytes rapidly increased (9 cases), because of resistance to ATRA (1 case), and development of organomegaly (1 case). The remaining patient died on day 6, from CNS bleeding. Apart from hyperleukocytosis, side effects were usually moderate. In the 11 patients who could be studied in vitro, a very good correlation was found between in vivo and vitro differentiation and proliferation of APL blasts with ATRA. Three patients were allografted after the “4 + 7” course. Four patients did not receive this course but received the subsequent “2 + 5” courses and maintenance. The remaining patients followed the scheduled protocol. Three patients relapsed after 8, 11, and 15 months (including one allografted patient). Two patients died in CR, after 6 and 17 months. The other 20 patients remained in CR after 18+ to 34+ months (median 21). Actuarial disease free interval (DFI) and event free survival (EFS) were 87% and 77%, respectively, after 18 months. These results were compared to those obtained in our previous APL 84 trial with chemotherapy alone in newly diagnosed APL (after excluding patients included in this trial who presented with hyperleukocytosis). In APL 84 trial, the CR rate was 76%, the actuarial DFI and EFS were 59% and 48% after 18 months, respectively. Differences with the pilot study of ATRA followed by chemotherapy were significant for DFI (P = .02), EFS (P = .006), but not for CR rate (P = .08). Although this is a historical comparison, these results suggest that ATRA followed by chemotherapy may prove superior to chemotherapy alone in newly diagnosed APL, by slightly increasing the CR rate, but perhaps more importantly by reducing the relapse rate.(ABSTRACT TRUNCATED AT 400 WORDS)

C/EBP Is Deregulated by PML-RAR in Acute Promyelocytic Leukemia.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 3015-3015
Author(s):  
Florence Guibal ◽  
Hanna S. Radomska ◽  
Lisa M. Johansen ◽  
Daniel G. Tenen
Keyword(s):  
Retinoic Acid ◽  
Fusion Protein ◽  
Acute Promyelocytic Leukemia ◽  
Promyelocytic Leukemia ◽  
Myeloid Differentiation ◽  
Computer Search ◽  
Granulocytic Differentiation ◽  
Transient Transfection Assay

Abstract Acute promyelocytic leukemia (APL) cells are blocked at the promyelocyte stage of myeloid differentiation. The majority of APL cells display the t(15;17) reciprocal chromosomal translocation leading to the expression of the fusion protein promyelocytic leukemia-retinoic acid receptor alpha (PML-RARa). Cells harboring this reciprocal translocation can be induced to differentiate after treatment with all-trans retinoic acid (at-RA) both in vivo and in vitro. During normal hematopoiesis, differentiation is regulated by several key transcription factors. One of them, CCAAT/enhancer binding protein alpha (C/EBPa), controls expression of genes regulating normal myeloid differentiation. Its disruption leads to a block of granulocytic differentiation. We thus hypothesize that C/EBPa could be deregulated in APL and therefore participate in the pathogenesis of APL. Using the U937PR9 cell line, which expresses an inducible PML-RARa, we observed that expression of PML-RARa induced a decrease of both C/EBPa mRNA and protein, leading to decreased C/EBPa DNA binding activity. Using a transient transfection assay with a C/EBPa promoter construct in presence or absence of PML-RARa, we are able to demonstrate that PML-RARa can repress C/EBPa promoter activity. This repression is specific to the fusion protein, as both PML and RARa have no effect upon the C/EBPa promoter. A computer search of the C/EBPa promoter sequence did not exhibit any evident RARE binding site, and therefore we are currently mapping the site(s) responsible for this repression. In conclusion, PML-RARa down regulates C/EBPa expression; this down regulation could participate in the pathogenesis of APL. This hypothesis is also supported by the observation that at-RA treatment of APL cell lines (NB4 and HT93) induces a rapid restoration of both C/EBPa RNA and protein. Thus, a decrease in both C/EBPa expression and activity could contribute to the differentiation block of APL cells by deregulating the normal myeloid differentiation program.

All-transretinoic acid followed by intensive chemotherapy gives a high complete remission rate and may prolong remissions in newly diagnosed acute promyelocytic leukemia: a pilot study on 26 cases

Blood ◽  
1992 ◽  
Vol 80 (9) ◽  
pp. 2176-2181 ◽  
Author(s):  
P Fenaux ◽  
S Castaigne ◽  
H Dombret ◽  
E Archimbaud ◽  
M Duarte ◽  
...  
Keyword(s):  
Pilot Study ◽  
Complete Remission ◽  
Acute Promyelocytic Leukemia ◽  
Remission Rate ◽  
Promyelocytic Leukemia ◽  
Intensive Chemotherapy ◽  
Newly Diagnosed ◽  
Historical Comparison

We entered 26 patients with newly diagnosed acute promyelocytic leukemia (APL) in a pilot study of all-transretinoic acid (ATRA) followed by intensive chemotherapy. Median age was 46 (range 25 to 63). No patient presented with leukocytes > 10 x 10(9)/L or had the microgranular APL variant. Cytogenetic analysis (25 patients) found a t(15;17) in 24 cases. Patients were scheduled to receive ATRA (45 mg/m2/d) until complete remission, followed by an intensive daunorubicin (DNR) + Ara C course (“4 + 7” course), then three “2 + 5” DNR + Ara C courses and maintenance chemotheapy. However, the “4 + 7” course was administered in emergency if hyperleukocytosis rapidly developed to prevent leukostasis. Twenty-five patients (96%) achieved CR, 14 with ATRA alone and 11 after the addition of the “4 + 7” course on day 2 to 30 of treatment, because leukocytes rapidly increased (9 cases), because of resistance to ATRA (1 case), and development of organomegaly (1 case). The remaining patient died on day 6, from CNS bleeding. Apart from hyperleukocytosis, side effects were usually moderate. In the 11 patients who could be studied in vitro, a very good correlation was found between in vivo and vitro differentiation and proliferation of APL blasts with ATRA. Three patients were allografted after the “4 + 7” course. Four patients did not receive this course but received the subsequent “2 + 5” courses and maintenance. The remaining patients followed the scheduled protocol. Three patients relapsed after 8, 11, and 15 months (including one allografted patient). Two patients died in CR, after 6 and 17 months. The other 20 patients remained in CR after 18+ to 34+ months (median 21). Actuarial disease free interval (DFI) and event free survival (EFS) were 87% and 77%, respectively, after 18 months. These results were compared to those obtained in our previous APL 84 trial with chemotherapy alone in newly diagnosed APL (after excluding patients included in this trial who presented with hyperleukocytosis). In APL 84 trial, the CR rate was 76%, the actuarial DFI and EFS were 59% and 48% after 18 months, respectively. Differences with the pilot study of ATRA followed by chemotherapy were significant for DFI (P = .02), EFS (P = .006), but not for CR rate (P = .08). Although this is a historical comparison, these results suggest that ATRA followed by chemotherapy may prove superior to chemotherapy alone in newly diagnosed APL, by slightly increasing the CR rate, but perhaps more importantly by reducing the relapse rate.(ABSTRACT TRUNCATED AT 400 WORDS)

scholarly journals Relationship between FLT3 mutation status, biologic characteristics, and response to targeted therapy in acute promyelocytic leukemia

Blood ◽  
2005 ◽  
Vol 106 (12) ◽  
pp. 3768-3776 ◽  
Author(s):  
Rosemary E. Gale ◽  
Robert Hills ◽  
Arnold R. Pizzey ◽  
Panagiotis D. Kottaridis ◽  
David Swirsky ◽  
...  
Keyword(s):  
Acute Promyelocytic Leukemia ◽  
Expression Profiles ◽  
Prognostic Significance ◽  
Promyelocytic Leukemia ◽  
Flt3 Mutation ◽  
Flt3 Inhibitor ◽  
Significant Difference ◽  
Flt3 Inhibitors ◽  
Wbc Count

The prognostic significance of FLT3 mutations in acute promyelocytic leukemia (APL) is not firmly established and is of particular interest given the opportunities for targeted therapies using FLT3 inhibitors. We studied 203 patients with PML-RARA–positive APL; 43% of the patients had an FLT3 mutation (65 internal tandem duplications [ITDs], 19 D835/I836, 4 ITD+D835/I836). Both mutations were associated with higher white blood cell (WBC) count at presentation; 75% of the patients with WBC counts of 10 × 109/L or greater had mutant FLT3. FLT3/ITDs were correlated with M3v subtype (P < .001), bcr3 PML breakpoint (P < .001), and expression of reciprocal RARA-PML transcripts (P = .01). Microarray analysis revealed differences in expression profiles among patients with FLT3/ITD, D835/I836, and wild-type FLT3. Patients with mutant FLT3 had a higher rate of induction death (19% vs 9%; P = .04, but no significant difference in relapse risk (28% vs 23%; P = .5) or overall survival (59% vs 67%; P = .2) at 5 years. In in vitro differentiation assays using primary APL blasts (n = 6), the FLT3 inhibitor CEP-701 had a greater effect on cell survival/proliferation in FLT3/ITD+ cells, but this inhibition was reduced in the presence of ATRA. Furthermore, in the presence of CEP-701, ATRA-induced differentiation was reduced in FLT3/ITD+ cells. These data carry implications for the use of FLT3 inhibitors as frontline therapy for APL.

scholarly journals Different Impact of Expression Levels of IGFBP2 and IGFBP7 on Survival and Relapse Rate in Acute Promyelocytic Leukemia

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 1382-1382
Author(s):  
Anna Hecht ◽  
Daniel Nowak ◽  
Florian Nolte ◽  
Verena Nowak ◽  
Julia Oblaender ◽  
...  
Keyword(s):  
Acute Promyelocytic Leukemia ◽  
Prognostic Marker ◽  
Relapse Rate ◽  
Conflicts Of Interest ◽  
Promyelocytic Leukemia ◽  
Control Group ◽  
High Dose ◽  
Healthy Controls ◽  
Expression Levels ◽  
Significant Difference

Abstract Introduction: Insulin-like growth factor binding proteins (IGFBP) are carriers of insulin-like growth factors (IGFs). They prolong their half-life and modulate their availability and activity. The IGF-signaling system has been shown to have an important role in various solid cancers and hematologic malignancies. High levels of IGFBP2 and IGFBP7 have been associated with chemoresistance, relapse and inferior survival in different leukemias. Acute promyelocytic leukemia (APL) is a distinct subtype of acute myeloid leukemia (AML), which has been reported to have increased expression of IGFBP2. However, there is no data on its impact on prognosis. In addition, no data exist on IGFBP7 in APL. The aim of this study was to elucidate the influence on prognosis of both candidate genes in APL patients. Methods: Expression levels of IGFBP2 und IGFBP7 were retrospectively analysed in bone marrow (BM) samples at the time of initial diagnosis from 69 APL patients (42 female, 27 male) after informed consent. Median age of patients was 46 years (range 19 to 82 years). All patients were diagnosed and treated in the German AML Cooperative Group (AMLCG) studies. Treatment consisted of simultaneous ATRA and double induction chemotherapy including high dose ara-C, one cycle of consolidation chemotherapy and 3 years monthly maintenance chemotherapy. In patients older than 60 years, the second induction cycle was at the discretion of the treating physician. Three patients (4%) received an induction of ATRA and an anthracycline without ara-C. BM samples of 22 healthy volunteers served as a control group. Multiplex reverse transcriptase quantitative real-time PCR (qRT-PCR) was performed on a LightCycler® 480 (Roche, Mannheim, Germany) PCR system. Glucose-6-phosphat isomerase was used as a housekeeping gene. For quantification of relative expression values a modified delta-delta CT calculation model according to Pfaffl was used after determination of PCR efficiencies. cDNA from the cell line K562 served as a calibrator in each run. All reactions were performed in triplicates. IGFBP2 expression groups were defined as follows: Patients with IGFBP2 expression below or equal the 25th percentile (IGFBP2low) were compared to patients with higher IGFBP2 expression (IGFBP2high). Overall survival (OS), relapse free survival (RFS) and the cumulative incidence of relapse (CIR) were calculated using the Kaplan-Meier method and a log-rank test was used to compare differences between the groups (p < 0.05). Results: Expression levels of IGFBP2 did not differ between APL patients and healthy controls. However, there was a significantly higher relapse rate in APL patients with low IGFBP2 expression (CIR: 25% in the IGFBP2low group vs. 5% in the IGFBP2high group; p=0.04). Accordingly, RFS of patients in the IGFBP2low group was also inferior (41% vs. 81% in the IGFBP2high group; p=0.0002; Fig. 1). The OS of patients who had responded to induction therapy was also influenced by IGFBP2 expression (OS of responders: 61% for IGFBP2low vs. 83% for IGFBP2high; p=0.02). However, there was no significant difference in the analysis of OS of all patients including patients who suffered early death. In contrast to these findings, IGFBP7 was expressed significantly lower in APL patients compared to healthy controls (p<0.0001) but there was no association with outcome of APL patients. Conclusion: Of the two analysed IGFBP family members only IGFBP2 showed impact on the prognosis of APL patients. Remarkably, IGFBP2 was not overexpressed compared to healthy controls in our patient cohort. The reason might be that whole BM samples of healthy controls were used instead of subpopulations. Still, among the APL patients cohort its expression showed a strong influence on prognosis especially on relapse rate and RFS. To find low expression as a negative prognostic marker is surprising as for leukemias only high expression has been reported as a negative factor. However, IGFBP2 has been proposed to suppress tumor development through binding IGFs and preventing IGF-receptor driven tumorigenesis. This is supported by the fact that the IGFBP2 promotor is hypermethylated in various types of cancer. In summary, we identified low IGFBP2 expression as a novel prognostic marker for APL. Further investigations are warranted to clarify its possible role in leukemia. Figure 1. Figure 1. Disclosures No relevant conflicts of interest to declare.

Mir-29c and Mir-424 Are Novel Myeloid Differentiation-Associated MicroRNAs in Acute Promyelocytic Leukemia.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 3346-3346
Author(s):  
Jasmin Batliner ◽  
Mathias Jenal ◽  
Martin F. Fey ◽  
Mario P. Tschan
Keyword(s):  
Acute Promyelocytic Leukemia ◽  
Cell Lines ◽  
Mirna Expression ◽  
Expression Patterns ◽  
Promyelocytic Leukemia ◽  
Mrna Levels ◽  
Atra Treatment ◽  
Granulocytic Differentiation ◽  
Blast Cells

Abstract MicroRNAs (miRNAs) are a class of small non-coding RNAs that regulate gene expression at the post-transcriptional level. Recent studies showed that they are critically involved in hematopoietic differentiation and function by a coordinating multi-target repression of hematopoiesis-related genes. To identify miRNAs involved in the pathogenesis of acute promyelocytic leukemia (APL), characterized by the t(15;17) translocation, we performed TaqMan Low Density Array-based miRNA expression profiling on blast cells from an APL patient under all-trans retinoic acid (ATRA) treatment. Although recent reports investigated miRNA expression patterns in APL blast cells and cell lines subjected to ATRA in vitro, to our knowledge this is the first study that relies on cells from an APL patient treated with ATRA in vivo. Since the downregulation of the PML-RARA transcript cannot be assessed within a time period of a few days, we monitored effective ATRA treatment by measuring mRNA downregulation of the panleukemic marker Wilms’ tumor (WT)-1. WT1 mRNA levels decreased 64% and 92% at day 3 and 6 upon ATRAtherapy, respectively. Total RNA obtained at diagnosis and at days 3/6 following ATRA therapy were screened for expression patterns of 384 human miRNAs including two endogenous controls, RNU44 and RNU48, for normalization of miRNA expression. Since these controls were regulated upon ATRA treatment, we normalized miRNA expression to miR-93, which showed stable expression in our samples. Consistent with previous in vitro APL miRNA profiling data, the granulocyte-specific miR-223 was induced 6.6-fold at day 6 upon ATRA treatment. For further analysis, we focused on two hematopoietic lineage-specific miRNAs, miR-29c and miR-424 that have not yet been associated with neutrophil development. miR-29c and miR-424 were upregulated 6.5- and 6.0-fold at day 6 in response to ATRA, respectively. Induction of these miRNAs was confirmed by individual real-time RT-PCR assays. Moreover, expression of miR-29c and miR-424 was further investigated in NB4 and HT93 APL cell lines. In both cell lines, miR-424 was upregulated in response to ATRA similar to the patient samples, suggesting a role for miR-424 in granulocytic differentiation in addition to that described in macrophage development. miR-29c, however, showed an upregulation in HT93 but not in NB4 cells implying cell type specific regulation. Additionally, we tested the involvement of miR- 29c in macrophage differentiation of HL60 leukemic cells using phorbol 12-myristate 13-acetate (PMA) as a differentiating agent. Interestingly, miR-29c showed an 8.0- fold upregulation similar to an 8.7-fold induction of miR-424, a known target of the transcription factor PU.1 upon PMA treatment. Based on the similar regulation of miR-29c and miR-424 and the presence of several putative PU.1 binding elements in the miR-29c promoter, we are currently investigating whether miR-29c is a novel transcriptional target of PU.1. A confirmed target of miR-29c is the protein DNA methyltransferase (DNMT 3A and 3B), which is overexpressed in myeloid leukemias. Therefore, induction of miR-29c during myelopoiesis might be needed to target DNMT. In conclusion, we propose a novel association of miR-29c and miR-424 with ATRA-induced neutrophil differentiation.

Comparative Study to Evaluate the Surface Detail Reproduction of Dental Stone after Immersion in Various Different Disinfectant Solutions, Under Stereomicroscope 10 X Magnification –An In-Vitro Study

2017 ◽  
Vol 9 (3) ◽  
Author(s):  
Rathika Rai ◽  
M. A. Easwaran ◽  
K. T. Dhivya
Keyword(s):  
Sodium Hypochlorite ◽  
In Vitro Study ◽  
Control Group ◽  
Immersion Method ◽  
Significant Difference ◽  
Surface Irregularities ◽  
Disinfectant Solution ◽  
Surface Detail ◽  
Group B

Aim: To evaluate the surface detail reproduction of dental stone this is immersed in different disinfectant solution and studied under stereomicroscope. Methodology: Total number of 30 specimens of dental stone (Type III) were made with measurements of 1.5cm diameter and 1cm height .This samples are divided in to 3 groups group A,B,C. were A is immersed in Distilled water which was taken as control group ;B is immersed in 2% Glutaraldehyde and C is immersed in 5%sodium hypochlorite. Each specimen were immersed in the disinfectant solution for 15 minutes and dried under room temperature for 24 hrs. After 24 hrs each specimens are studied under stereomicroscope for surface details. Result: The results showed no significant difference in the surface irregularities and porosities for a group 1 and group 2 except group 3 which showed significant increase in the porosities, surface irregularities and erosions after disinfection with 5% NaHOCl by immersion method. Conclusion: The surface detail reproduction capacity of die stone was adversely affected when 5% Sodium hypochlorite was used as disinfectant solution when compare d to control group and 2% Glutaraldehyde

Sign in / Sign up

Export Citation Format

Share Document