Rare form of leukemia found to originate in stem cells

February 13, 2014 by Bob Yirka report
A Wright's stained bone marrow aspirate smear from a patient with precursor B-cell acute lymphoblastic leukemia. Credit: VashiDonsk/Wikipedia

(Medical Xpress)—An international team of researchers working out of the University of Toronto has found that one type of rare leukemia appears to get its start in stem cells. In their paper published in the journal Nature, the team describes how they were able to identify haematopoietic stem cells and what it may mean for future treatment of the cancer. Nicole Potter and Mel Greaves offer an in-depth explanation of the work done by the team in a News & Views piece in the same journal.

Leukemia is cancer of the bone marrow or blood—it presents itself as an overabundance of white blood cells that have not matured. Because they are not able to carry out normal blood functions, the patient, if left untreated, dies because the properly functioning cells are crowded out by the cancerous cells. One rare type of leukemia, called acute myeloid leukemia (AML) is unique in that it gets its start in the blood forming tissues within bone marrow—it's also particularly aggressive.

Scientists have known about stem cells that eventually form into white or red blood cells (or platelets) for a couple of decades, what's new in this study is the identification of a specific type of stem (haematopoietic) cell that appears to at times mutate, causing AML, and that it tends to appear as a result of mutations of a specific gene—DNMT3a.

Research by the team has revealed that up to 25 percent of AML patients have the mutation—they've found that in addition to causing cancerous cells to develop, it also causes the (pre-leukemic) stem cells to behave in ways similar to cells that develop into normal blood cells, which allows for surviving chemotherapy. That means that a patient diagnosed with leukemia, who goes through chemo which results in remission of the leukemia, could find themselves having a relapse—that it happens, is obviously very bad news for patients, but that the researchers have uncovered how the pre-leukemic cells come to exist and how they survive is very good news. It means that tests can be developed to look for the mutated gene and then therapies developed that can target the specific hematopoietic stem cells before they mature into cancerous cells.

Explore further: Researchers discover how a mutated protein outwits evolution and fuels leukemia

More information: Identification of pre-leukaemic haematopoietic stem cells in acute leukaemia, Nature (2014) doi:10.1038/nature13038

Abstract
In acute myeloid leukaemia (AML), the cell of origin, nature and biological consequences of initiating lesions, and order of subsequent mutations remain poorly understood, as AML is typically diagnosed without observation of a pre-leukaemic phase. Here, highly purified haematopoietic stem cells (HSCs), progenitor and mature cell fractions from the blood of AML patients were found to contain recurrent DNMT3A mutations (DNMT3Amut) at high allele frequency, but without coincident NPM1 mutations (NPM1c) present in AML blasts. DNMT3Amut-bearing HSCs showed a multilineage repopulation advantage over non-mutated HSCs in xenografts, establishing their identity as pre-leukaemic HSCs. Pre-leukaemic HSCs were found in remission samples, indicating that they survive chemotherapy. Therefore DNMT3Amut arises early in AML evolution, probably in HSCs, leading to a clonally expanded pool of pre-leukaemic HSCs from which AML evolves. Our findings provide a paradigm for the detection and treatment of pre-leukaemic clones before the acquisition of additional genetic lesions engenders greater therapeutic resistance.

Related Stories

KIT researchers develop artificial bone marrow

January 10, 2014

Artificial bone marrow may be used to reproduce hematopoietic stem cells. A prototype has now been developed by scientists of KIT, the Max Planck Institute for Intelligent Systems, Stuttgart, and Tübingen University. The ...

New target isolated for leukemia drug development

February 11, 2014

There are potentially effective treatments for acute myeloid leukemia (AML), but they only work in 20 to 40 percent of cases. In a paper published today in Leukemia, a Nature journal, a UT Health Science Center researcher ...

Recommended for you

Study examines evolution of cancer

February 8, 2016

A novel Yale study answers age-old questions about how cancers spread by applying tools from evolutionary biology. The new insights will help scientists better understand the genetic origins of tumor metastases, and lead ...

The growing menace of HPV‑related throat and mouth cancers

February 2, 2016

There's a new cancer epidemic on the rise. It's an aggressive throat and mouth cancer caused by the human papillomavirus (HPV)—the same sexually transmitted virus that leads to cervical cancer—but it's affecting mostly ...

How gut inflammation sparks colon cancer

February 4, 2016

Chronic inflammation in the gut increases the risk of colon cancer by as much as 500 percent, and now Duke University researchers think they know why.

1 comment

Adjust slider to filter visible comments by rank

Display comments: newest first

ginseng
not rated yet Feb 13, 2014

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.