Insights into Acute Myeloid Leukemia: Critical Analysis on its Wide Aspects

2020 ◽  
pp. 1-9
Keyword(s):  
Myeloid Leukemia ◽  
Deep Understanding ◽  
New Drugs ◽  
Induction Treatment ◽  
Information Network ◽  
Self Renewal ◽  
Disease Biology ◽  
The Subject ◽  
Health Research And Development ◽  
Acute Myeloid

Acute myeloid leukaemia (AML) is a heterogeneous, most common type of acute leukaemia that involves mutation in haematopoietic and progenitors stem cells (HPSCs) leading to uncontrolled division, self-renewal and differentiation. Though it was untreatable about a half century ago, AML is now considered to be treatable in up to 40% of adults and those who are at or under 60 years of age. For the post-induction treatment, the mutation testing and cytogenetics are still an important prognostic tool. The AML treatment remains unchanged for almost three decades, although the field is advanced with the discovery of new drugs and deep understanding of the disease biology. Still, many people are relapsing and are dying eventually from the disease. This review discusses the broader aspects of AML, reflecting some of the most important and productive areas of research on the subject and was conducted using thoroughly searching databases, including Health Research and Development Information network Plus (HERDIN Plus), google scholar and PubMed to critically analyses the recent advances, available treatments and future prospectives of AML.

scholarly journals New and Emerging Targeted Therapies for Pediatric Acute Myeloid Leukemia (AML)

Children ◽  
2020 ◽  
Vol 7 (2) ◽  
pp. 12 ◽  
Author(s):  
Jing Chen ◽  
Chana L. Glasser
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Kinase Inhibitors ◽  
New Drugs ◽  
Drug Conjugates ◽  
Disease Biology ◽  
Care Guidelines ◽  
Multi Agent ◽  
Acute Myeloid ◽  
Refractory Aml

The relapse rate for children with acute myeloid leukemia (AML) remains high despite advancements in risk classification, multi-agent chemotherapy intensification, stem cell transplantation, and supportive care guidelines. Prognosis for this subgroup of children with relapsed/refractory AML remains poor. It is well known that the ceiling of chemotherapy intensification has been reached, limited by acute and chronic toxicity, necessitating alternative treatment approaches. In the last several years, our improved understanding of disease biology and critical molecular pathways in AML has yielded a variety of new drugs to target these specific pathways. This review provides a summary of antibody drug conjugates (ADCs), small molecule inhibitors, and tyrosine kinase inhibitors with an emphasis on those that are currently under clinical evaluation or soon to open in early phase trials for children with relapsed/refractory AML.

scholarly journals A KDM4A-PAF1-mediated epigenomic network is essential for acute myeloid leukemia cell self-renewal and survival

2021 ◽  
Vol 12 (6) ◽  
Author(s):  
Matthew E. Massett ◽  
Laura Monaghan ◽  
Shaun Patterson ◽  
Niamh Mannion ◽  
Roderick P. Bunschoten ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Cell Activity ◽  
Leukemia Cell ◽  
Gene Signature ◽  
Pathological Feature ◽  
Self Renewal ◽  
Stem Cell Activity ◽  
Molecular Mechanism Of Action ◽  
Acute Myeloid

AbstractEpigenomic dysregulation is a common pathological feature in human hematological malignancies. H3K9me3 emerges as an important epigenomic marker in acute myeloid leukemia (AML). Its associated methyltransferases, such as SETDB1, suppress AML leukemogenesis, whilst H3K9me3 demethylases KDM4C is required for mixed-lineage leukemia rearranged AML. However, the specific role and molecular mechanism of action of another member of the KDM4 family, KDM4A has not previously been clearly defined. In this study, we delineated and functionally validated the epigenomic network regulated by KDM4A. We show that selective loss of KDM4A is sufficient to induce apoptosis in a broad spectrum of human AML cells. This detrimental phenotype results from a global accumulation of H3K9me3 and H3K27me3 at KDM4A targeted genomic loci thereby causing downregulation of a KDM4A-PAF1 controlled transcriptional program essential for leukemogenesis, distinct from that of KDM4C. From this regulatory network, we further extracted a KDM4A-9 gene signature enriched with leukemia stem cell activity; the KDM4A-9 score alone or in combination with the known LSC17 score, effectively stratifies high-risk AML patients. Together, these results establish the essential and unique role of KDM4A for AML self-renewal and survival, supporting further investigation of KDM4A and its targets as a potential therapeutic vulnerability in AML.

scholarly journals RSPO2 inhibits BMP signaling to promote self-renewal in acute myeloid leukemia

Cell Reports ◽  
2021 ◽  
Vol 36 (7) ◽  
pp. 109559
Author(s):  
Rui Sun ◽  
Lixiazi He ◽  
Hyeyoon Lee ◽  
Andrey Glinka ◽  
Carolin Andresen ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Bmp Signaling ◽  
Self Renewal ◽  
Acute Myeloid

scholarly journals The Polycomb complex PRC2 supports aberrant self-renewal in a mouse model of MLL-AF9;NrasG12D acute myeloid leukemia

Oncogene ◽  
2012 ◽  
Vol 32 (7) ◽  
pp. 930-938 ◽  
Author(s):  
J Shi ◽  
E Wang ◽  
J Zuber ◽  
A Rappaport ◽  
M Taylor ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Mouse Model ◽  
Myeloid Leukemia ◽  
Self Renewal ◽  
Polycomb Complex ◽  
Acute Myeloid

scholarly journals Target Therapy in Acute Myeloid Leukemia

2020 ◽  
Author(s):  
Vasko Graklanov
Keyword(s):  
Clinical Trials ◽  
Acute Myeloid Leukemia ◽  
Elderly Patients ◽  
Acute Leukemia ◽  
Mechanism Of Action ◽  
Myeloid Leukemia ◽  
Target Therapy ◽  
New Drugs ◽  
Cytotoxic Treatment ◽  
Acute Myeloid

Acute myeloid leukemia (AML) is the most common form of acute leukemia in elderly patients. Over the past four decades the basic therapeutic armamentarium was the standard cytotoxic treatment. The new insights in understanding the pathogenesis of AML was the momentum that revolutionized the treatment landscape in AML. The last five years unprecedented growth has been seen in the number of target therapy drugs for the treatment of AML. These new drugs did not just have a clinical benefit as single agents but also have improved AML patient outcomes if combined with conventional cytotoxic therapy. Here, we review recent advances in target-based therapy for patients with AML focusing on their mechanism of action and the results from already published clinical trials.

New drugs creating new challenges in acute myeloid leukemia

2019 ◽  
Vol 58 (12) ◽  
pp. 903-914 ◽  
Author(s):  
Ing S. Tiong ◽  
Andrew H. Wei
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
New Drugs ◽  
New Challenges ◽  
Acute Myeloid

Mitoxantrone, etoposide, and intermediate-dose cytarabine: an effective and tolerable regimen for the treatment of refractory acute myeloid leukemia.

1991 ◽  
Vol 9 (7) ◽  
pp. 1210-1214 ◽  
Author(s):  
S Amadori ◽  
W Arcese ◽  
G Isacchi ◽  
G Meloni ◽  
M C Petti ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Response Rate ◽  
Induction Treatment ◽  
Front Line ◽  
Resistant Disease ◽  
Nonhematologic Toxicity ◽  
Lower Response Rate ◽  
Refractory Acute Myeloid Leukemia ◽  
Acute Myeloid

Thirty-two patients with refractory acute myeloid leukemia (AML) received salvage therapy with a single course of mitoxantrone 6 mg/m2 intravenous (IV) bolus, etoposide 80 mg/m2 IV for a period of 1 hour, and cytarabine (Ara-C) 1 g/m2 IV for a period of 6 hours daily for 6 days (MEC). Eighteen patients were primarily resistant to conventional daunorubicin and Ara-C induction treatment; eight patients had relapsed within 6 months from initial remission; six patients had relapsed after a bone marrow transplantation (BMT) procedure. Overall, 21 patients (66%) achieved a complete remission (CR), two (6%) died of infection during induction, and nine (28%) had resistant disease. Age greater than 50 years was the only factor predictive for a significantly lower response rate (P = .03). The median remission duration was 16 weeks; the overall median survival was 36 weeks. Severe myelosuppression was observed in all patients resulting in fever or documented infections in 91% of patients. Nonhematologic toxicity was minimal. We conclude that the MEC regimen has significant antileukemic activity and acceptable toxicity in salvage AML. Its benefit in front-line AML therapy is being investigated.

scholarly journals A randomized study of high-dose cytarabine in induction in acute myeloid leukemia [see comments]

Blood ◽  
1996 ◽  
Vol 87 (5) ◽  
pp. 1710-1717 ◽  
Author(s):  
JF Bishop ◽  
JP Matthews ◽  
GA Young ◽  
J Szer ◽  
A Gillett ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Univariate Analysis ◽  
Disease Free Survival ◽  
Dose Effect ◽  
Induction Treatment ◽  
High Dose ◽  
Remission Duration ◽  
High Dose Cytarabine ◽  
Acute Myeloid

Abstract High-dose cytarabine (ara-c) may overcome cytarabine resistance in leukemic blasts. It has been used as a successful salvage and in postremission therapy but not as initial induction treatment. Patients aged 15 to 60 years, presenting with newly diagnosed acute myeloid leukemia (AML) were randomized to receive either high-dose cytarabine, 3 g/m2 12 hourly on days 1, 3, 5, and 7 for 8 doses, daunorubicin 50 mg/m2 days 1 to 3, etoposide 75 mg/m2 days 1 to 7, (HIDAC-3–7) or standard dose cytarabine 100 mg/m2 continuous intravenous infusion for 7 days with daunorubicin and etoposide at the same dose and schedule as above (7–3–7). Patients could receive a second or third induction course if complete remission (CR) was not achieved. All patients received the same postinduction consolidation therapy (5–2–5) for 2 courses. Eligible patients had no prior chemotherapy or myelodysplastic disease. Patients have been followed for a median of 4.5 years. Of 301 patients treated, complete response (CR) was achieved in 71% with HIDAC- 3–7 and 74% with 7–3–7. For patients in CR, the estimated median remission duration was 45 months with HIDAC-3–7 and 12 months with 7–3– 7 (P = .0005 univariate analysis, P = .0004 multivariate analysis). The estimated percentage of patients relapse free 5 years after achieving a CR was 49% on HIDAC-3–7 and 24% on 7–3–7. Patients in CR tended to survive longer with HIDAC-3–7 but there were no overall survival differences between the two arms. HIDAC-3–7 was associated with significantly more toxicity in induction with more leukopenia, thrombocytopenia, nausea, and vomiting and eye toxicity (all P < .001) but a similar incidence of severe central nervous system and cerebellar toxicity compared to 7–3–7. The consolidation treatment was the same in both arms but caused significantly more leukopenia and thrombocytopenia in patients previously treated with HIDAC-3–7 induction (P < .0001). We conclude that a dose-effect exists for cytarabine in AML and that HIDAC- 3–7 prolongs remission duration and disease-free survival and is tolerable when used as initial induction therapy in patients with de novo AML.

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