Chromosomal abnormality of acute promyelocytic leukemia other than PML-RARA: a case report of acute promyelocytic leukemia with del(5q)
3
Citation
18
Reference
10
Related Paper
Citation Trend
Abstract:
The recent study described a better outcome in acute promyelocytic leukemia patients treated with all-trans retinoic acid and arsenic oxide compared to those treated with all-trans retinoic acid combined with conventional chemotherapy. The pivotal study indicated that favorable-risk acute promyelocytic leukemia patients can be cured without any cytotoxic chemotherapy. Even high-risk patients are treatable with cytotoxic agents. Acute promyelocytic leukemia does not develop only by the dedifferentiation caused by PML-RARA. A determined oncogene other than PML-RARA which promotes cell proliferation would be required. We recently treated a 30-year-old Japanese female who achieved molecular remission with only the administration of all-trans retinoic acid. The patient’s leukemic clones concomitantly had a del(5q) aberrant chromosome with t(15;17) (q22;q12). The patient’s bone marrow cells indicated clonal evolution of the tumor cells expressing CD13dim, CD33+, CD117+, and lacking HLA-DR, CD34 and CD11b. A fluorescence in situ hybridization analysis detected PML-RARA fusion genes in the patient’s bone marrow specimens, leading to the diagnosis of acute promyelocytic leukemia. A del(5q) is one of the characteristic chromosomal abnormalities observed in myelodysplastic syndrome. On the other hand, up to 40 % of acute promyelocytic leukemia cases are known to harbor the addition of a clonal cytogenetic abnormality. However, such a case acute promyelocytic leukemia with del(5q) would be rare, rather than myelodysplastic syndrome, consequently obtaining t(15;17). Which cytogenetic abnormalities, acute promyelocytic leukemia or myelodysplastic syndrome, came first is informative to make a clinical decision for the initial therapy. In this case, we speculated the PML-RARA translocation is an original pathogenesis and thereafter additional cytogenetic abnormalities (del(5q) and -6) common in myelodysplastic syndrome. All-trans retinoic acid lead the patient into molecular remission. We propose that an assessment of additional cytogenetic abnormality in acute promyelocytic leukemia would contribute to the clinical decisions regarding whether to treat disease with all-trans retinoic acid and cytotoxic agents. It would be of interest to know the extent of cytogenetic abnormality in the patients regarding to mixed leukemia. One or more additional cytogenetic abnormalities other than PML-RARA could account for the biological malignant grade and prognostic index.Keywords:
Promyelocytic leukemia protein
Arsenic Trioxide
CD117
To explore the combination therapy of all-trans retinoic acid (ATRA) and arsenic trioxide (ATO, As2O3) on acute promyelocytic leukemia (APL).A meta-analysis of six studies was performed. Among 415 included cases, 165 cases were in the ATRA + ATO group, 129 cases in the ATRA-alone group, and 121 cases in the ATO-alone group. The complete remission (CR) rate and incidences of three groups were compared, respectively, between the therapies of ATRA + ATO with ATRA-alone, ATRA + ATO with ATO-alone, and ATRA with ATO.The assessment results showed that ATRA + ATO therapy significantly improved the CR rate and decreased the incidences of cutaneous reaction compared with ATRA-alone (P < 0.05). However, incidence of liver injury was higher in the ATRA + ATO and ATO-alone groups than that in ATRA-alone group (P < 0.05). Difference in the complications between ATRA + ATO therapy and ATO-alone was not significant (P > 0.05).In conclusion, we suggest low-dose ATRA and ATO combination therapy may be more effective for the treatment of APL.
Arsenic Trioxide
Tretinoin
Cite
Citations (14)
Arsenic Trioxide
Differentiation Therapy
Promyelocytic leukemia protein
Promyelocyte
Tretinoin
Cite
Citations (22)
Arsenic Trioxide
Promyelocytic leukemia protein
Tretinoin
Differentiation Therapy
Cite
Citations (42)
Acute promyelocytic leukemia (APL) is a subtype of acute myeloid leukemia (AML) characterized by the reciprocal translocation of t(15;17) (q22;q21) encoding the promyelocytic leukemia–retinoic acid...
Arsenic Trioxide
Promyelocytic leukemia protein
Tretinoin
Cite
Citations (4)
Mechanistic effects of arsenic trioxide on acute promyelocytic leukemia and other types of leukemias
Abstract Acute promyelocytic leukemia (APL), a subtype of acute myeloid leukemia characterized with a translocation between promyelocytic leukemia gene (PML) on chromosome 15 and retinoic acid receptor alpha gene (RARα) on chromosome 17. Transcription of this fusion gene results in PML/RARα fusion protein blocking expression of critical genes involved in differentiation of myeloid cells through interaction with RAR element. PML/RARα fusion protein prevents normal function of PML and RARα as well as inhibiting apoptosis. Arsenic trioxide (ATO) is an important agent for the treatment of relapsed and newly diagnosed APL. ATO induces apoptosis, autophagy, and partial cellular differentiation as well as inhibiting cell growth and angiogenesis. Recognition of signaling pathways and molecular mechanisms induced by ATO can be effective for discovering novel treatment strategies to target leukemia cells. Also, it can be developed for the treatment of a variety of cancer cells. This review provides a perspective on anticancerous effects of ATO on APL and leukemia cells.
Arsenic Trioxide
Promyelocytic leukemia protein
Differentiation Therapy
Cite
Citations (15)
To summarize limitations involved in arsenic trioxide therapeutic effects in acute promyelocytic leukemia, because current studies show that some individuals of acute promyelocytic leukemia have relatively poor outcomes during treatment with arsenic trioxide.Most relevant articles were included in the PubMed database between 2000 and 2013 with the keywords "acute promyelocytic leukemia," "arsenic trioxide," "thiol" or "methylation." In addition, a few older articles were also reviewed.Data and articles related to arsenic trioxide effect in acute promyelocytic leukemia treatment were selected and reviewed. We developed an overview of limitations associated with arsenic trioxide therapeutic effect.This review focuses on the researches about the arsenic trioxide therapeutic effect in acute promyelocytic leukemia and summarizes three mainly limitations which can influence the arsenic trioxide therapeutic effect to different degrees. First, with the combination of arsenic and glutathione the therapeutic effect and cytotoxicity decrease when glutathione concentration increases; second, arsenic methylation, stable arsenic methylation products weaken the apoptosis effect of arsenic trioxide in leukemia cells; third, gene mutations affect the sensitivity of tumor cells to arsenic trioxide and increase the resistance of leukemia cells to arsenic trioxide.The chief limitations are listed in the review. If we can exclude all of them, we can obtain a better therapeutic effect of arsenic trioxide in patients with acute promyelocytic leukemia.
Arsenic Trioxide
Therapeutic effect
Cite
Citations (7)
Arsenic Trioxide
Promyelocytic leukemia protein
Tretinoin
Cite
Citations (1)
Objective:To observe the arsenic trioxide (As2O3) combined with alltransretinoic acid (ATRA) treatment of acute promyelocytic leukemia (APL) of the efficacy and toxicity.Methods: 21 patients with acute promyelocytic leukemia (APL) patients with doubleAs2O3 combined ATRA induction therapy,patients with high white blood cell with a single chemotherapy drug third year plus tipshirt ester base (H) or daunorubicin (DNR).Results:In 21 patients,19 cases of complete remission,complete remission (CR) rate of 90.47%;1 patient died of intracranial hemorrhage.Conclusion:arsenic trioxide combined with alltrans retinoic acid treatment of acute promyelocytic leukemia precise and well tolerated in patients.
Arsenic Trioxide
Daunorubicin
White blood cell
Tretinoin
Cite
Citations (0)
Objective To study the effect of all-trans retinoic acid(ATRA)combined with arsenic trioxide for acute promyelocytic leukemia.Methods 24 cases were selected who had been diagnosed with acute promyelocytic leukemia,by the way of clinical diagnosis,blood,bone marrow,cell immunity,cellular genetics and other tests.One group was treated with ATRA combined with arsenic trioxide,another group was treated with arsenic trioxide.Clinical effective was compared between two groups.Results Laboratory parameters and complete remission rate of combined group were better than monotherapy group,there was significant difference between two groups(P0.05).Conclusion ATRA pluses arsenic trioxide for acute promyelocytic leukemia,can increase complete remission rate and survival rate,which is an effective treatment method.
Arsenic Trioxide
Tretinoin
Cite
Citations (0)
Arsenic Trioxide
Promyelocytic leukemia protein
Cite
Citations (29)