Different Kinetics of WT1 and PML-RAR α Gene Expression Levels during Remission Induction Therapy with All- trans Retinoic Acid Alone in Acute Promyelocytic Leukemia

2006 ◽  
Vol 84 (5) ◽  
pp. 468-470 ◽  
Author(s):  
Hiroya Tamaki ◽  
Tamotsu Yamagami ◽  
Manabu Kawakami ◽  
Eui Kim ◽  
Machiko Mishima ◽  
...  
Keyword(s):  
Gene Expression ◽  
Retinoic Acid ◽  
Acute Promyelocytic Leukemia ◽  
Induction Therapy ◽  
Promyelocytic Leukemia ◽  
Remission Induction ◽  
Trans Retinoic Acid ◽  
All Trans Retinoic Acid ◽  
Kinetics Of ◽  
Gene Expression Levels

Long-term Follow-up of Hemostatic Molecular Markers during Remission Induction Therapy with All-Trans Retinoic Acid for Acute Promyelocytic Leukemia

1997 ◽  
Vol 77 (04) ◽  
pp. 641-645 ◽  
Author(s):  
Reiko Watanabe ◽  
Mitsuru Murata ◽  
Nobuyuki Takayama ◽  
Michihide Tokuhira ◽  
Masahiro Kizaki ◽  
...  
Keyword(s):  
Molecular Markers ◽  
Retinoic Acid ◽  
Acute Promyelocytic Leukemia ◽  
Induction Therapy ◽  
Promyelocytic Leukemia ◽  
Bleeding Complications ◽  
Remission Induction ◽  
Inhibitor Complex ◽  
Trans Retinoic Acid ◽  
All Trans Retinoic Acid

SummaryHemostatic molecular markers were serially monitored in a prospective fashion during remission induction therapy with all-trans retinoic acid (ATRA) in sixteen patients with acute promyelocytic leukemia (APL). One patient with leukocytosis before treatment and three patients who later developed hyperleukocytosis also received chemotherapy with behenoyl Ara-C and daunorubicin. Plasma levels of E-fragment of fibrin and fibrinogen degradation product (FDP-E), FDP-D dimer (D-D), thrombin-antithrombin complex (TAT), and plasmin-α2 plasmin inhibitor complex (PIC) were markedly elevated in all but one patient before treatment, and these parameters decreased to normal or near normal ranges in most patients within the first 7 days of treatment. Interestingly, we have found that these parameters were again elevated during the later course of ATRA therapy (after day +7) in eleven patients for various reasons including cytotoxic chemotherapy (3 cases), fever (5 cases; 2 cases with apparent infection, 3 cases without known etiology), Caesarean section (1 case), and no apparent etiology (2 cases). Three patients showed bleeding complications during reelevation of molecular markers, but none developed thrombosis. Plasma elastase-α1 proteinase inhibitor complex (E-α1PI) was markedly elevated in all patients at diagnosis and did not decrease significantly during ATRA therapy. Plasma tissue factor antigen was mildly elevated in one out of four patients studied, and thrombomodulin was elevated in two out of ten patients tested. These results confirmed the rapid normalization of coagulopathy during the early phase of remission induction therapy with ATRA but suggest that re-elevation of molecular markers occurs frequently during the later course of ATRA therapy.

scholarly journals All-trans-retinoic acid–induced pseudotumor cerebri in acute promyelocytic leukemia

2014 ◽  
Vol 05 (03) ◽  
pp. 273-275
Author(s):  
T. M. Anoop ◽  
Nidhi Jain ◽  
Sreejith G. Nair ◽  
Geetha Narayanan
Keyword(s):  
Retinoic Acid ◽  
Acute Promyelocytic Leukemia ◽  
Induction Therapy ◽  
Treatment Strategy ◽  
Pseudotumor Cerebri ◽  
Promyelocytic Leukemia ◽  
Trans Retinoic Acid ◽  
All Trans Retinoic Acid

ABSTRACTAll-trans-retinoic acid is an integral part in the treatment strategy of acute promyelocytic leukemia (APL). Here we describe a case of pseudotumor cerebri associated with all-trans-retinoic acid (ATRA) during the induction therapy in an adult with acute promyelocytic leukemia (APL).

scholarly journals Resistance to all-trans retinoic acid (ATRA) therapy in relapsing acute promyelocytic leukemia: study of in vitro ATRA sensitivity and cellular retinoic acid binding protein levels in leukemic cells [see comments]

Blood ◽  
1993 ◽  
Vol 82 (7) ◽  
pp. 2175-2181 ◽  
Author(s):  
L Delva ◽  
M Cornic ◽  
N Balitrand ◽  
F Guidez ◽  
JM Miclea ◽  
...  
Keyword(s):  
Retinoic Acid ◽  
Acute Promyelocytic Leukemia ◽  
Induction Therapy ◽  
Binding Protein ◽  
Promyelocytic Leukemia ◽  
Leukemic Cells ◽  
Differentiation Induction ◽  
Trans Retinoic Acid ◽  
All Trans Retinoic Acid

Abstract All-trans retinoic acid (ATRA) induces leukemic cell differentiation and complete remission (CR) in a high proportion of patients with acute promyelocytic leukemia (AML3 subtype). However, relapses occur when ATRA is prescribed as maintenance therapy, and resistance to a second ATRA-induction therapy is frequently observed. An induced hypercatabolism of ATRA has been suggested as a possible mechanism leading to reduced ATRA sensitivity and resistance. CRABPII, an RA cytoplasmic binding protein linked to RA's metabolization pathway, is induced by ATRA in different cell systems. To investigate whether specific features of the AML3 cells at relapse could explain the in vivo resistance observed, we studied the CRABP levels and in vitro sensitivity to ATRA of AML3 cells before and at relapse from ATRA. Relapse-AML3 cells (n = 12) showed reduced differentiation induction when compared with “virgin”-AML3 cells (n = 31; P < .05). Dose-response studies were performed in 2 cases at relapse and showed decreased sensitivity to low ATRA concentrations. CRABPII levels and in vitro differentiation characteristics of AML3 cells before and at relapse from ATRA therapy were studied concomittantly in 4 patients. High levels of CRABPII (median, 20 fmol/mg of protein) were detected in the cells of the 4 patients at relapse but were not detected before ATRA therapy. Three of these patients showed a decrease in differentiation induction of their leukemic cells, and a failure to achieve CR with a second induction therapy of ATRA 45 mg/m2/day was noted in all patients treated (n = 3). Results from this study provide evidence to support the hypothesis of induced-ATRA metabolism as one of the major mechanisms responsible for ATRA resistance. Monitoring CRABPII levels after ATRA withdrawal may help to determine when to administer ATRA in the maintenance or relapse therapy of AML3 patients.

scholarly journals Combining gene mutation with gene expression analysis improves outcome prediction in acute promyelocytic leukemia

Blood ◽  
2019 ◽  
Vol 134 (12) ◽  
pp. 951-959 ◽  
Author(s):  
Antonio R. Lucena-Araujo ◽  
Juan L. Coelho-Silva ◽  
Diego A. Pereira-Martins ◽  
Douglas R. Silveira ◽  
Luisa C. Koury ◽  
...  
Keyword(s):  
Gene Expression ◽  
Retinoic Acid ◽  
Acute Promyelocytic Leukemia ◽  
Gene Expression Analysis ◽  
Outcome Prediction ◽  
Prognostic Score ◽  
Promyelocytic Leukemia ◽  
Alternative Therapies ◽  
Trans Retinoic Acid ◽  
All Trans Retinoic Acid

Abstract Luceno-Araujo et al use assays of mutations associated with myeloid malignancy to propose an integrative prognostic score for acute promyelocytic leukemia (ISAPL) in patients treated with all-trans retinoic acid and anthracycline-based therapy. They demonstrate that the ISAPL is superior for predicting outcomes and identifying patients who may benefit from alternative therapies to maximize their chance of a cure.

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