The co‐expression of <i>PML/RAR α</i> and <i>AML1/ETO</i> fusion genes is associated with ATRA resistance

Lima, Rodrigo Siqueira de Abreu e; Baruffi, Marcelo Rozera; Lima, Agnaldo Soares; Oliveira, Fábio Morato de; Figueiredo-Pontes, Lorena Lôbo de; Tone, Luíz Gonzaga; Rogatto, Sílvia Regina; Falcão, Roberto Passetto; Chauffaille, Maria de Lourdes Ferrari; Rego, Eduardo Magalhães

doi:10.1111/j.1365-2141.2004.05343.x

Cited by 9 publications

(3 citation statements)

References 9 publications

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“…The co-existence of t(15;17) and t(8;21) in a single leukemic clone is a very rare finding and the results of the few reported cases are conflicting. However, it has been proposed that PML-RARa and AML1/ETO fusion proteins may mutually affect their pathogenetic mechanism, rendering the cells resistant to ATRA which is in agreement with the resistance of our patient to ATRA based treatment 38,80,81…”

Section: Discussionsupporting

confidence: 89%

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Acute Promyelocytic Leukemia: An Experience on 95 Greek Patients Treated in the All-Trans-Retinoic Acid Era

Pagoni

Garofalaki

Panitsas³

et al. 2011

Mediterr J Hematol Infect Dis

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Acute promyelocytic leukemia (APL) is highly curable with the combination of all-transretinoic acid (ATRA) and anthracycline based chemotherapy, but the percentage of early deaths remains high. In the present study, we report the clinical, immunophenotypic, cytogenetic and molecular characteristics and outcome of APL patients diagnosed and treated in various Hospitals of Greece and Cyprus.We describe the data of ninety-five APL patients who were diagnosed during the last 15 years. Seven (7.4%) newly diagnosed APL patients died due to intracranial hemorrhage within 72 hours of presentation. All but two patients were induced with ATRA alone or ATRA plus chemotherapy. The early death rate was 14.9%. After induction all 80 evaluable patients achieved complete hematologic remission. The cumulative incidence of relapse was 18.3%. Eight of the ten relapsed patients were successfully salvaged, while both patients with molecularly resistant disease died during salvage treatment. Overall survival (OS) at 5 years was 78.4% and disease free survival (DFS) 73.6%. In multivariate analysis of OS age over 60 years, DIC at diagnosis and marginally major hemorrhage at presentation were identified as adverse prognostic factors. In the subgroup of patients with available data on FLT3 mutation status (49 out of 94), ITD positivity also remained as an independent prognostic factor in the final model of OS, together with major hemorrhage and marginally high Sanz score. We found a close correlation between the CD2 expression and the development of the differentiation syndrome (DS). In conclusion, the main problem in managing patients with APL is still the high early death rate.

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Section: Discussionsupporting

confidence: 89%

“…One patient showed t(8;21) in addition to t(15;17). He was treated with a hybrid protocol (AIDA and a conventional AML protocol) but he never achieved molecular CR 80,81. There was not any difference between the patients with ACAs and those without ACAs concerning the clinical features (data not shown) or the response to treatment 11,15…”

Section: Resultsmentioning

confidence: 98%

Acute Promyelocytic Leukemia: An Experience on 95 Greek Patients Treated in the All-Trans-Retinoic Acid Era

Pagoni

Garofalaki

Panitsas³

et al. 2011

Mediterr J Hematol Infect Dis

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“…Treatment with ATRA alone for 40 days induced complete hematological remission in one patient [194], whereas others have reported that coexpression of the t(15;17), and the t(8;21) encoded fusion proteins can be associated with ATRA resistance [195]. …”

Section: The Prognostic Impact Of T(8;21) In Human Amlmentioning

confidence: 99%

Acute Myeloid Leukemia with the t(8;21) Translocation: Clinical Consequences and Biological Implications

Reikvam

Hatfield

Kittang

et al. 2011

BioMed Research International

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The t(8;21) abnormality occurs in a minority of acute myeloid leukemia (AML) patients. The translocation results in an in-frame fusion of two genes, resulting in a fusion protein of one N-terminal domain from the AML1 gene and four C-terminal domains from the ETO gene. This protein has multiple effects on the regulation of the proliferation, the differentiation, and the viability of leukemic cells. The translocation can be detected as the only genetic abnormality or as part of more complex abnormalities. If t(8;21) is detected in a patient with bone marrow pathology, the diagnosis AML can be made based on this abnormality alone. t(8;21) is usually associated with a good prognosis. Whether the detection of the fusion gene can be used for evaluation of minimal residual disease and risk of leukemia relapse remains to be clarified. To conclude, detection of t(8;21) is essential for optimal handling of these patients as it has both diagnostic, prognostic, and therapeutic implications.

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Simultaneous occurrence of two distinct leukemic clones with PML-RARα and RUNX1-RUNX1T1 in a case of acute myeloid leukemia

et al. 2017

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The co‐expression of PML/RAR α and AML1/ETO fusion genes is associated with ATRA resistance

Cited by 9 publications

References 9 publications

Acute Promyelocytic Leukemia: An Experience on 95 Greek Patients Treated in the All-Trans-Retinoic Acid Era

Acute Promyelocytic Leukemia: An Experience on 95 Greek Patients Treated in the All-Trans-Retinoic Acid Era

Acute Myeloid Leukemia with the t(8;21) Translocation: Clinical Consequences and Biological Implications

Simultaneous occurrence of two distinct leukemic clones with PML-RARα and RUNX1-RUNX1T1 in a case of acute myeloid leukemia

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