جستجوی مقالات مرتبط با کلیدواژه « acute promyelocytic leukemia » در نشریات گروه « پزشکی »

 Acute promyelocytic leukemia (APL) is a type of aggressive acute myeloid leukemia (AML), characterized by the presence of abnormal promyelocytes in the bone marrow and bloodstream. The abnormal promyelocytes found in APL can lead to severe complications such as bleeding and blood clot formation.

 A 7-year-old boy diagnosed with APL encountered a unique occurrence of isolated molecular relapse following a recent episode of SARS-CoV-2 infection while undergoing routine monitoring for treatment response. The relapse was confirmed by the detection of the PML/RARalpha gene abnormality in both the peripheral blood and bone marrow samples. Notably, during relapse, the boy displayed symptoms indicative of a cerebral ischemic stroke; however, effective management was achieved through the administration of low molecular weight heparin (LMWH) and corticosteroids. Subsequently, the patient underwent an allogenic bone marrow transplantation. Of note, throughout an 18-month period of close monitoring, no complications were reported.

 The detection of the PML-RARA transcript in peripheral blood can serve as a valuable tool for detecting isolated molecular relapse in pediatric APL. In cases where patients are undergoing immunosuppressive chemotherapy, the presence of neurological signs and symptoms may be the sole indicator of APL relapse, and it can be thoroughly investigated through the use of MRI with or without diffusion-weighted imaging (DWI). The administration of LMWH is a safe treatment strategy until D-dimer levels return to normal. It has been observed that COVID-19, as seen with other respiratory viruses, may potentially contribute to the relapse of pediatric APL, highlighting its significance in disease progression.

Wilms’ tumor gene 1 (WT1) gene mutation has been reported to be a prognostic factor in normalcytogenetic acute myeloid leukemia (AML) patients. Higher rates of mutation in the WT1 gene have been reported in several tumors including normal-cytogenetic AML patients. Data regarding WT1 mutations in acute promyelocytic leukemia (APL) is very scarce. In this study, we evaluated the incidence and impact of WT1 mutation on the outcome of APL patients.

A total of 92 patients diagnosed with APL were studied in three distinct groups: early mortality, relapsed, and persistent complete remission. Genomic DNA of bone marrow samples of patients was analyzed. For quantification of expression levels of the WT1 gene, real-time quantitative PCR (rqPCR) was performed by a real-time PCR system. WT1 mutation and its impact on prognosis were considered the primary endpoint of the study. Statistical analysis was performed with STATA.

WT1 mutation frequency was 6.25% in the early mortality group (1/16 patients), 13.16% in the relapse group (5/38 patients), and 7.89% in the persistent complete remission group (3/38 patients). 8 mutations were in exon 7 and one mutation in exon 9. WT1 mutation in the relapse group was associated with a trend toward worse disease-free survival (DFS) while overall survival (OS) was not affected by WT1 mutation in univariate analysis. Patients with no mutations in WT1 and FLT3/ITD had better overall survival and diseasefree survival compared to patients with mutations in the WT1 gene or FLT3/ITD in the relapse group.

The frequency of WT1 gene mutations does not differ significantly between patients with early mortality, relapse, and persistent complete remission. The presence of WT1 mutation is associated with higher relapse and lower survival rates in relapse group patients.

The rate of survival in acute promyelocytic leukemia (APL) can dramatically improve, if the patients receive all-trans-retinoic acid (ATRA) treatment. However, this drugchr('39')s toxicity is a major problem in APL treatment. Previous researches have demonstrated that phyto-polyphenols such as epigallocatechin gallate (EGCG) and kaempferol cause apoptosis in hematopoietic neoplasms, but do not negatively impact healthy cells. The present study compared the differentiation effects of kaempferol and EGCG, as well as ATRA in NB4 leukemia cells during five days.

Herein, kaempferol and EGCGchr('39')s differentiation-inducing activity was examined by NBT assay and Real-time PCR in leukemia NB4 cells.

EGCG (25 µM) and kaempferol (50 µM) induced the NB4 cellschr('39') differentiation, towards a granulocytic pattern similar to ATRA (1 μM). EGCG further suppressed PML/RARα clinical markerchr('39')s expression compared to kaempferol, it also decreased HDAC1 expression in leukemia NB4 cells.

 Based on this study, compared to kaempferol, EGCG at low concentrations is preferred for long-term ATRA therapy in APL patients.

SARS-CoV-2 infection is spreading worldwide, and due to multi-organ involvement, it could mimic other well-known diseases.

Herein, we describe the case of a pediatric patient with acute promyelocytic leukemia (APL), who developed severe respiratory illness with diffuse pulmonary involvement after consuming all-transretinoic acid during the COVID-19 pandemic.

All-transretinoic acid syndrome is a very similar condition to COVID-19 both in clinical presentations and radiologic findings; thus, the treatment of such patients may be challenging.

Acute promyelocytic leukemia (APL) with t(15;17)(q22;q12) is a relatively common subtype of acute myeloid leukemia (AML).  Here, our objective was to ascertain the survival of patients with this leukemia in north-east of Iran.

Survival rates of 42 APL patients with t(15;17)(q22;q12) were assessed. Clinical information was obtained from archived medical records. Statistical analysis was performed by SPSS 18 software using log-ranked test and Kaplan Maier survival analysis.

Females and males comprised 49% and 51%, respectively. The mean age at diagnosis was 34.3 14.1 years old. During the study period, 17 demises occurred in males, while this number was 7 in females. The mean survival of patients (month) was 23.22 3.57 (95% CI: 16.21 30.2).  The five-year survival rate obtained 30%. Regarding demographic and clinical features, the highest rates of 5-year survival were recorded in patients with 20-35 years old (47.6%), males (51%), white blood cell count 140 /l (100%).

Younger age, lower WBC count and higher platelet count were significantly associated with longer survival in AML patients with t(15;17)(q22; q12).

DNA methylation is an epigenetic modification that has the ability to alter gene expression and function. These epigenetic changes have been associated with the development of cancer. Previous research has found that DNA methylation patterns can predict disease prognosis for patients with Acute Promyelocytic Leukemia (APL). The role of DNMT1 and CDH1 in regulating the extension of cells are studied in this study.

DNA was extracted from peripheral blood samples of APL patients and treated with bisulfite. DNMT1 and CDH1 gene promoter methylation was subsequently analyzed using methylation-specific PCR (MSP). Real-time PCR was used to measure the expression level of DNMT1 and CDH1 genes.

Partial methylation of the CDH1 gene promoter was detected in 20% of APL patients and an unmethylated status was detected in 80% of patient samples. Additionally, an unmethylated status in the DNMT1 gene promoter was detected in 100% of APL patient samples.

Our study found the CDH1 gene promoter to be unmethylated in almost all APL patients, while the DNMT1 promoter was unmethylated in all APL patients. Furthermore, we observed an increase in both CDH1 and DNMT1 gene expression in APL patients compared to healthy controls. These findings suggest that DNMT1 may not have a specific role in inhibiting CDH1 gene expression in APL. Applying higher resolution techniques would help to better uncover the DNA methylation patterns in patients with APL. Further research is required to determine the role of DNA methylation and CDH1 and DNMT1 gene expression in APL.

Acute promyelocytic leukemia (APL) is a subtype of acute myeloid leukemia (AML). APL is famed with some special blood coagulation disorders such as disseminated intravascular coagulation (DIC). The therapeutic methods of APL contain All Trans Retinoic Acid (ATRA), arsenic trioxide (ATO) or/and chemotherapy. Many studies have been done on APL blood disorders and its treatment. These studies have shown different results. In this systematic article, we tried to review the effect of ATO therapy with or without ATRA and chemotherapy on DIC parameters (D.dimer, Prothrombin Time, Activated Partial Thrombin Time, Platelet count) in APL patients. The result of included studies demonstrated that although ATO can reduce the number of malignant cells in the bone marrow and peripheral blood, it does not have enough potential to attenuate the danger of high score DIC that is usual in APL patients and should be better to be used with other therapeutic methods.

Acute promyelocytic leukemia represents a medical emergency with a high rate of early mortality. It has a high predilection for disseminated intravascular coagulation and in the absence of treatment, can be rapidly fatal. Without treatment, the median survival is less than 1 month.The coagulopathy in APL is complex and can be attributed to a combination of thrombocytopenia, disseminated intravascular coagulation and hyperfibrinolysis. White blood cell count at presentation is an important predictor of early hemorrhagic death. With the discovery of all-trans retinoic acid and arsenic trioxide, acute promyelocytic leukemia has transformed from a devastating disease into one of the most curable malignancies.Patients should be monitored for the development of differentiation syndrome, seen in 25 % of patients within 2-21 days of initiation of treatment. Early death is still a key issue, particularly in the elderly population, reiterating the importance of rapid diagnosis and treatment.We report the case of a 48 year-old-male diagnosed with the microgranular variant of acute promyelocytic leukemia M3 subtype and treated with all-trans retinoic acid and arsenic trioxide who achieved complete hematological remission.

There are different treatment protocols available for acute promyelocytic leukemia (APL) such as all-trans retinoic acid (ATRA) plus chemotherapy or arsenic trioxide (ATO) based regimens. In this study, we focused on the role of ATRA followed by an anthracycline-containing chemotherapy regimen. This study reported the outcome of APL patients at 501 army hospital; Tehran, Iran. Seventy-three patients were included between 1995 and 2015. Treatment in our center for the majority of cases included induction with ATRA followed by Cytarabine (AraC) and an anthracycline agent (daunorubicin), and then three cycles of consolidation chemotherapy. Maintenance consisted of a 2-year period of medication with ATRA, Methotrexate (MTX) and 6-mercaptopurine (6-MP). Relapsed cases were treated with ATRA and a combination of etoposide, mitoxantrone, and cytarabine. Kaplan-Meier estimate was used to calculate survival rates. We detected 5- and 10-year overall and disease-free survival rates of 51.6% and 50.2% respectively. For those patients who survived induction deaths and received ATRA-based chemotherapy the 5-year OS and DFS rates were 68.8% and 66.5%, respectively. Hematologic complete remission (CR) was observed in all but three patients, and relapse occurred in 12 cases. The cardinal causes of induction death were disseminated intravascular coagulation (DIC) and infection. Up to the end of the follow-up time, 31 patients died including 11 cases of the relapsed disease. The combination of ATRA and chemotherapy could lead to an acceptable CR rate and relapse incidences in newly diagnosed APL patients, but more effective strategies need to be developed for screening and treatment of relapse.

Acute Promyelocytic Leukemia (APL) is a subclass of acute myeloid leukemia. The chromosomal aberration in 95% of APL cases is t(15; 17) (q22; q21), which prevents cell differentiation. Characterization of the underlying molecular lesion is valuable in determining optimal treatment strategy. The goal of this study was to develop a new and powerful Flow- FISH technique to detect the long isoform (L) of PML-RARa fusion transcript in NB4 cell line.
To achieve the best condition for fixation, two different fixatives including 2% paraformaldehyde and 75% ethanol were used. 0.2% Triton X-100 and 0.2% saponin were used for the permeabilization step .In hybridization, a wide range of times and temperatures were used and probe was designed in FRET system. Results were confirmed by fluorescent microscope assay and reverse transcription PCR.
In the present study, a novel technique was successfully optimized that combines in situ hybridization with flow cytometry to detect the presence of PML-RARa transcript. Using standard fixation and permeabilization protocol of 2% PFA and 0.2% saponin gave the best fluorescent results in flow cytometry. Also, results indicated that the optimum time and temperature for hybridization was 2 hr at 42oC. The results of reverse transcription PCR and fluorescent microscopy confirmed the presence of PML-RARa transcript.
The concordance between the results of Flow-FISH and those of two other techniques including reverse transcription PCR and FISH indicated that this method would be applicable as a diagnostic test for APL in clinical samples and MRD monitoring.

Acute promyelocytic leukemia (APL) is a hematopoietic malignancy that is known with its special cytogenetic feature. Several studies have surveyed expression signature of microRNAs (miRNAs) in APL patients, especially patients who are treated with conventional therapy of this disease. Using miRNAs as diagnostic or prognostic biomarkers in various cancers has been widely studied. Currently, most studies are focusing on exploiting miRNAs as therapeutic tools, and promising progress has been achieved in this field. Recently, studies in the field of miRNA‑based therapy in APL have been started.

Acute promyelocytic leukemia (APL) is a unique subtype of acute leukemia. APL is a curable disease; however, drug resistance, early mortality, disease relapse and treatment-related complications remain challenges in APL patient management. One issue underlying these challenges is that the molecular mechanisms of the disease are not sufficiently understood.
In this study, we performed a meta-analysis of gene expression profiles derived from microarray experiments and explored the background of disease by functional and pathway analysis.
Our analysis revealed a gene signature with 406 genes that are up or down-regulated in APL. The pathway analysis determined that MAPK pathway and its involved elements such as JUN gene and AP-1 play important roles in APL pathogenesis along with insulin-like growth factor–binding protein-7.
The results of this meta-analysis could be useful for developing more effective therapy strategies and new targets for diagnosis and drugs.