Deciphering the Therapeutic Resistance in Acute Myeloid Leukemia.

International Journal of Molecular Sciences
Carmelo GurnariValeria Visconte

Abstract

Acute myeloid leukemia (AML) is a clonal hematopoietic disorder characterized by abnormal proliferation, lack of cellular differentiation, and infiltration of bone marrow, peripheral blood, or other organs. Induction failure and in general resistance to chemotherapeutic agents represent a hindrance for improving survival outcomes in AML. Here, we review the latest insights in AML biology concerning refractoriness to therapies with a specific focus on cytarabine and daunorubicin which still represent milestones agents for inducing therapeutic response and disease eradication. However, failure to achieve complete remission in AML is still high especially in elderly patients (40-60% in patients >65 years old). Several lines of basic and clinical research have been employed to improve the achievement of complete remission. These lines of research include molecular targeted therapy and more recently immunotherapy. In terms of molecular targeted therapies, specific attention is given to DNMT3A and TP53 mutant AML by reviewing the mechanisms underlying epigenetic therapies' (e.g., hypomethylating agents) resistance and providing critical points and hints for possible future therapies overcoming AML refractoriness.

References

Aug 17, 2000·Journal of the National Cancer Institute·P BorstJ Wijnholds
Jul 13, 2002·Trends in Biochemical Sciences·Boudewijn M T Burgering, Geert J P L Kops
Aug 15, 2002·Blood·D Gary Gilliland, James D Griffin
Dec 18, 2004·Current Opinion in Hematology·Guido MarcucciClara D Bloomfield
Jan 26, 2005·British Journal of Haematology·Markus SchaichUNKNOWN SHG AML96 Study Group
Oct 18, 2005·Cornea·Toshio SudaShigeto Shimmura
Feb 4, 2006·Blood·Frederick R AppelbaumStephen H Petersdorf
Jul 25, 2006·Nature·Andrei V KrivtsovScott A Armstrong
Oct 22, 2009·Pharmacogenomics·Jatinder K Lamba
Nov 12, 2010·The New England Journal of Medicine·Timothy J LeyRichard K Wilson
Feb 2, 2011·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Eric J FeldmanArthur C Louie
Sep 29, 2011·Seminars in Oncology·Tapan M KadiaHagop Kantarjian
Nov 19, 2011·Nature Reviews. Genetics·Manel Esteller
Mar 8, 2013·Journal of Molecular Biology·Irina V NovikovaKarissa Y Sanbonmatsu
May 1, 2013·Leukemia·C MeyerR Marschalek
Jan 11, 2014·British Journal of Haematology·Yoko Tabe, Marina Konopleva
Apr 23, 2014·International Journal of Cancer. Journal International Du Cancer·Hong WangJi-Fan Hu
Apr 26, 2014·Blood·Theresa PlackeStefan Fröhling
Apr 30, 2014·Annual Review of Biophysics·Frederick C Streich, Christopher D Lima
May 2, 2014·Frontiers in Immunology·Chang-Sook HongMichael Boyiadzis
May 14, 2014·Bone Marrow Research·Ningning HeZongjin Li
May 23, 2014·Journal of Cellular Biochemistry·Kimberly N KremerKaren E Hedin
Jan 1, 2015·Blood·R Coleman LindsleyBenjamin L Ebert
Jun 30, 2015·Experimental Hematology·Chun-Wei Chen, Scott A Armstrong

❮ Previous
Next ❯

Citations

Jul 25, 2021·International Journal of Molecular Sciences·Alvina I KhamidullinaAlexandra V Bruter

❮ Previous
Next ❯

Methods Mentioned

BETA
xenograft
MethylTransferase
ubiquitination
MDS

Software Mentioned

PETHEMA

Related Concepts

Related Feeds

AML: Role of LSD1 by CRISPR (Keystone)

Find the latest rersearrch on the ability of CRISPR-Cas9 mutagenesis to profile the interactions between lysine-specific histone demethylase 1 (LSD1) and chemical inhibitors in the context of acute myeloid leukemia (AML) here.

Acute Myeloid Leukemia

Acute myeloid leukemia (AML) is a clinically and genetically heterogeneous disease with approximately 20,000 cases per year in the United States. AML also accounts for 15-20% of all childhood acute leukemias, while it is responsible for more than half of the leukemic deaths in these patients. Here is the latest research on this disease.