The promyelocytic leukemia (PML) tumor suppressor of acute promyelocytic leukemia (APL) is essential for a number of proapoptotic and growth-suppressive pathways as well as for the activity of differentiating agents such as retinoic acid (RA). In human APL, the dose of PML is reduced to heterozygosity given that one allele is involved in the chromosomal translocation while the status of the remaining PML allele is unknown. We have therefore used single-strand conformational polymorphism (SSCP) and sequencing analysis to screen DNA from APL patients for mutations at the PML locus. We identified DNA sequence variations resulting in a truncated PML protein in APL cases that displayed RA resistance and a very poor prognosis. Mutation analysis also led to the identification of aberrant PML sequence variations in other hematopoietic malignancies. Complete functional loss of PML is therefore selected by the APL phenotype and associates with poor prognosis and RA unresponsiveness.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1182/blood-2003-07-2200 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Telomere shortening in donor cell-derived acute promyelocytic leukemia after allogeneic hematopoietic stem cell transplantation: a case report.
Ann Hematol
January 2025
Hematology Division, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital, 3-18-22 Honkomagome, Bunkyo-Ku, Tokyo, 113-8677, Japan.
Donor cell leukemia (DCL), in which malignancy evolves from donor's stem cells, is an infrequent complication of allogeneic hematopoietic stem cell transplantation. Acute promyelocytic leukemia (APL) derived from donor cell is extremely rare and only four cases have been reported to date. Herein we report a case of donor cell-derived APL developing 32 months after haploidentical peripheral blood stem cell transplantation using posttransplant cyclophosphamide for myelodysplastic syndromes.
View Article and Find Full Text PDFClinicopathologic and Molecular Characterization of NUP98-Rearranged Acute Leukemias.
Int J Lab Hematol
January 2025
Department of Pathology, University of Texas Southwestern Medical Center, Dallas, Texas, USA.
Introduction: NUP98 rearrangements are rare in acute leukemias and portend a poor prognosis.
Methods: This study explored clinicopathologic and molecular features of five patients with NUP98 rearranged (NUP98-r) acute leukemias, including three females and two males with a median age of 34 years.
Results: NUP98 fusion partners were associated with distinctive leukemia characteristics and biology.
Zebrafish modeling of atypical PML-RARA isoform from acute promyelocytic leukemia patient and its implications for clinical treatment.
Ann Hematol
January 2025
Department of Hematology, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou, 510180, China.
Acute promyelocytic leukemia (APL) is driven by the specific fusion gene PML-RARA produced by chromosomal translocation. Three classic isoforms, L, V, and S, are found in more than 95% of APL patients. However, atypical PML-RARA isoforms are usually associated with uncertain disease progression and treatment prognosis.
View Article and Find Full Text PDFThe clinical observation of none-promyelocytic AML patients inducted with idarubicin or daunorubicin included standard regimens: a tertiary care center experience.
BMC Pharmacol Toxicol
January 2025
Department of Hematology, Zhujiang Hospital of Southern Medical University, No. 253, Gongye Road, Haizhu District, Guangzhou, 510280, China.
Background: Few Chinese study compared the impacts of idarubicin and daunorubicin based "3+7" intensive chemotherapies on early and long-term outcomes of AML patients through exploring their real-world data.
Patients And Methods: Our none promyelocytic AML patients inducted with "3+7" regimens were studied to find out the factors relating with induction response and long term survival.
Results: Idarubicin induction was related with less chemotherapy refractory rate comparing with daunorubicin induction (10% vs 25%, P = 0.
FHL1 as a prognostic biomarker and therapeutic target in acute promyelocytic leukaemia.
Discov Oncol
January 2025
Basic Medical School, Southwest Medical University, Luzhou, 646000, Sichuan, People's Republic of China.
Acute myeloid leukemia (AML) has a poor prognosis and high heterogeneity. Most cases of leukemias are caused by environmental factors interacting with the cell's genetic material, but treatment is still dominated by cell cycle drugs. Therefore, there is an urgent need to find reliable biomarkers.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!