Independent researchers cite using Cellero primary human immune cells in their recently published study on the mechanisms underlying development of acute myeloid leukemia. [1]

This publication represents a broad collaborative effort across a number of renowned research institutes, including Memorial Sloan Kettering and Fred Hutchinson Cancer Research Centers, and Cornell University. The research team want nothing less than to determine how leukemia develops; not simply the genes involved, but the concrete mechanisms by which those genes become dysfunctional.

Acute myeloid leukemia (AML) is an aggressive cancer that starts in the bone marrow and can quickly move into the blood and spread to other parts of the body. While AML accounts for only 1% of all cancers, the toll it takes on human lives is heavier than any clinical statistics can signify.

Gene dysregulation is at the core of how human cancers develop, and AML is no exception. But since different subtypes of childhood and adult AML display different gene abnormalities, finding a treatment for a broad range of patients has seemed an impossible task. This is why the team decided on a different approach. The scientists wanted to find the unifying mechanism whereby genes become dysregulated in the first place, driving a normal cell to become a cancer cell.

Based on past research, the team felt sure that the answer involved transcription factor MYB and its primary co-factor, CBP/P300. MYB functions as a “master regulator” of gene expression in many different cell types, including hematopoietic cells. It also just happens to be the most significantly required gene in 37 distinct leukemia cell lines and is essential to their growth and survival.

The researchers developed a synthetic peptide that selectively interferes with binding between MYB and its co-factor. They used various forms of that peptide to study the interaction of MYB with other co-factors that form various transcription complexes, and ultimately with the genes controlling immune cell growth and differentiation.

The scientists relied on Cellero to supply the normal human primary immune cells they needed to assess the effect of their proposed treatment on healthy hematopoietic cell types. Cellero offers a wide inventory of primary human isolated immune cells for clinical and pre-clinical research. Cellero collects blood and immune cell products in compliance with protocols reviewed and approved by an independent review board (IRB). All Cellero cell products are:

  • Tested for cell count, viability, and function
  • Tested negative for blood-borne pathogens
  • Purified and characterized by flow cytometric analysis
  • High-resolution HLA-typed (if applicable)
  • Characterized by FcγRIII genotype (if available)

For this study, the researchers used Cellero healthy donor B cells, cytotoxic T cells, and monocytes. They wanted to know whether the specific blockade of MYB-CBP/P300 transcription machinery would have a deleterious effect on normal hematopoietic cell differentiation and function.

The scientists were able to demonstrate that specific MYB transcription complex co-factors are aberrantly expressed and assembled in AML cell lines as compared to normal human blood cells. By examining protein expression levels via Western blot, they found that most transcription complex co-factors that are assembled with MYB are also present in normal immune cells. However, not only are certain co-factors more abundantly expressed in AML cells, but specific combinations of these factors are only present in AML cells. This suggests that the inappropriate expression and assembly of these co-factors are what lead to abnormal gene expression and abnormal growth and differentiation in leukemia cells.

Using the synthetic peptide to specifically blockade MYB interactions with aberrantly expressed co-factors resulted in minimal effects on the growth of normal immune progenitor cells, but significant suppression of growth and survival of AML cell lines. The scientists were also able to use various forms of the synthetic peptide to map out MYB complex assembly with a wide variety of co-factors.

This work is a huge leap forward in understanding the underlying mechanisms of AML development. It is one of the first studies to provide high-resolution maps of MYB transcription complex assembly and protein-protein interactions specific to AML cells. These co-factor interactions should make promising targets for improved AML therapies.

At Cellero, we are proud to provide high-quality immune cell products in support of ongoing cancer research. Please visit our website to learn more about our immune cell product line.

 

Reference:

Takao S., et al. Convergent organization of aberrant MYB complex controls oncogenic gene expression in acute myeloid leukemia. eLife. Feb 2021.

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