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Proteins in Acute Myeloid Leukaemia Support Precision Medici...
Ageing and Longevity, Article, Precision Medicine, Wellbeing

Proteins in Acute Myeloid Leukaemia Support Precision Medicine

Advances in our understanding of leukemogenesis have enabled more accurate prognostication and therapy changes that have improved survival rates.

Small molecule antagonists of pathogenic mutant proteins have been investigated in well-designed clinical studies and are now authorized for use in the diagnosis of Acute Myeloid Leukemia (AML), either alone or in conjunction with chemotherapy.

The earliest effort to define the prognosis of sufferers based on morphology and cytochemical stains was the French-American-British classification of AML.

Further modifications in classification were made when chromosomal analysis (conventional metaphase karyotyping and fluorescence in situ hybridization) improved.

The capacity to recognize particular mutations in AML and target these alterations has resulted in the most exciting developments.

What exactly are proteins?

Protein is a very complex molecule found in all living things.

Proteins have a high nutritional value and play a direct role in the chemical reactions that keep life going.

Proteins were identified as important by chemists in the early nineteenth century, notably Swedish scientist Jöns Jacob Berzelius, who created the name protein in 1838, a word derived from the Greek precios, which means “the first position.”

Proteins are species-specific, meaning that one species’ proteins differ from those of another. Amino acid makeup and sequence are comparable in proteins with similar functions.

What is acute myeloid leukemia, and what is its significance?

Cancerous cells can arise in almost any region of the body.

Leukemias are malignancies that begin in cells that would usually grow into various blood cell types.

Leukemia usually begins in the early stages of white blood cells, however, it can also begin in other types of blood cells.

There are numerous kinds of leukemia, which are classified primarily by whether the disease is acute (rapidly progressing) or chronic (slowly progressing), as well as whether it begins in myeloid or lymphoid cells.

Acute myeloid leukemia (AML) begins in the bone marrow (the soft inner portion of some bones where new blood cells are formed), but it usually spreads swiftly to the bloodstream.

It can affect other organs such as the lymph nodes, liver, spleen, central nervous system (brain and spinal cord), and testicles.

AML is most commonly caused by cells that would normally convert into white blood cells (other than lymphocytes), although it can also occur in other types of blood-forming cells.

AML Subtypes and Prognostic Factors discuss the many types of AML.

AML also known as acute myelocytic leukemia, acute myelogenous leukemia, acute granulocytic leukemia, and acute non-lymphocytic leukemia, is a kind of acute myeloid leukemia.

How do proteins play a role in AML?

In acute myeloid leukemia, the protein RNF5 performs a unique function.

RNF5 interacts with a second cell protein termed RBBP4 to regulate the expression of genes linked in AML, rather than its expected job of identifying aberrant proteins for elimination.

These results, which were reported in Nature Communications, have major implications for improving the outcomes of AML patients.

  • RNF5 functions as a ubiquitin ligase, which aids in the degradation of other proteins.
  • However, this study discovered that in AML cells, RNF5 acquires a new capability via collaborating with the epigenetic regulator RBBP4.
  • RNF5 alters RBBP4 rather than degrades it, affecting its recruitment to regulate the expression of genes linked to AML growth.
  • “Finding this ubiquitin ligase is really controlling gene transcription in AML was rather surprising for us,” says Ali Khateb, Ph.D., a postdoctoral investigator in the Ronai group and the paper’s lead author.
  • The researchers found more evidence that RNF5 and RBBP4 act together to cause AML.
  • Patients’ specimens from the United States and Israel were analyzed.
Photo by National Cancer Institute on Unsplash

Cytokines and cytokine receptors on cancer cells

Cytokines are molecular transmitters that allow immune system cells to interact with one another in order to produce a coordinated, powerful, yet self-contained reaction to a specific antigen.

Increased attempts to define cytokines and utilize their extensive signaling networks to develop cancer therapies have paralleled the rising interest in leveraging the immune system to destroy cancer during the last two decades.

The purpose of this study is to describe the basic biology and clinical uses of the main cytokines used in cancer immunotherapy.

The paper will also discuss new cytokines in preclinical production, biological agent combos, innovative delivery methods, and prospective future cytokine research paths.

A novel precision medicine-based therapy for AML!

RNF5 functions as a ubiquitin ligase, which aids in the degradation of other proteins.

However, this study discovered that in AML cells, RNF5 acquires a new capability via collaborating with the epigenetic regulator RBBP4.

RNF5 alters RBBP4 rather than degrades it, affecting its recruitment to regulate the expression of genes linked to AML growth.

“Finding this ubiquitin ligase is really controlling gene transcription in AML was rather surprising for us,” says Ali Khateb, Ph.D., a postdoctoral researcher in the Ronai group and the paper’s lead author.

The researchers found more evidence that RNF5 and RBBP4 act together to cause AML.

Patients’ samples from the United States and Israel were analyzed.

These discoveries, according to Khateb, might have numerous therapeutic implications. Scientists could enhance targeted treatments and advance precision medicine by suppressing RNF5.

“It’s likely that individuals with lower levels of RNF5 or RBBP4 would react favorably to HDAC inhibitors,” Ronai added. “Based on RNF5 or RBBP4 expression, we may be able to predict which AML patients would react to these therapies.”

To wrap things up

Identifying the prognostic impact of particular mutations and developing therapies that target these variants has resulted in enormous advances in the treatment of AML.

In sufferers with newly diagnosed and R/R FLT3-mutated AML, tailored novel molecular inhibitors targeting mutant FLT3 have enhanced overall survival.

Likewise, individuals with R/R IDH1/2 AML who receive IDH1/2 inhibitors appear to have a high remission rate with few side effects.

MRD evaluation might assist speed up the approval of treatments in the future.

MRD testing provides for early therapy adjustment in individuals who do not react to treatment and early detection in those who do.

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