Cell Stem Cell: Gene deletions behind abnormalities in blood cancer cells

The mystery of why the control centers, or nuclei, of some blood cancer cells have apparently strange shapes is being solved

These new research findings provide clues to the origin and development of these cancers, and may provide ways to diagnose and treat certain leukemias earlier

These nuclei squeezed in the middle, similar to pince-nez glasses, are known as Pelger-Hu?t anomalies

Although this structural change inside blood cells suggests that it could be cancer, until a recent study, no one knew what caused it to happen

In the journal Cell Stem Cell, cancer biologists report the discovery of the genetic mutation behind this cellular abnormality

Even in the age of genomic medicine, the initial diagnosis of many cancers still centers on the appearance of cells under the microscope

Pap smears are just one example of cancer screening, which looks for irregularly shaped nuclei in a patient's cells, he said

One of Duratov's own research interests is the study of malignant tumors of infection-fighting white blood cells called neutrophils

What determines the fate of these progenitor cells that lead to the emergence of cancer cells rather than normal neutrophils? While they are still pluripotent and capable of producing any of the various blood cell types, neutrophils, red blood cells, or The progenitor cells of platelets are called myeloid cells

The myeloid cells themselves sometimes develop abnormal precancerous lesions

"Lamins are proteins that line the interior of the cell nucleus and are mutated in genetic diseases -- well-known as progeria, a disease that accelerates aging," Doulatov explained

"We found that depletion of lamin B1 resulted in defects in nuclear morphology and in human hematopoietic stem cells associated with malignancy," the researchers noted

His team went on to detail that lamin B1 deficiency alters genome organization

They also showed that abnormal nuclei in the patient's myeloid precancerous cells were associated with a deletion of chromosome 5q that spanned the B1 region

According to the researchers, the absence of lamin B1 is a necessary and sufficient factor for Pelger-Hu?t abnormalities
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The scientists were also able to link this abnormal nuclear shape to the fate of progenitor and hematopoietic stem cells determined by genome organization
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The study also shows that lamin B1 is a master regulator of cell fate specification in hematopoietic stem cells, as well as a master regulator of genome integrity and nuclear morphology, according to the researchers
.

Summarizing the recent findings, Doulatov said, "We show that lamin B1 deletion leads to alterations in stem cell function, nuclear shape, and leukemia progression
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Our study identifies lamin mutations in cancer and demonstrates that these mutations are associated with oddly shaped mutations.
The nuclei are involved, and over the past century, these nuclei have puzzled and helped pathologists identify cancer
.
"

The latest genomic findings and their impact on abnormal transformation of hematopoietic cells may be important in future leukemia care
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The presence of these changes could be an early cancer biomarker whose detection could enable early diagnosis and treatment of leukemia, the researchers said
.

article title

Lamin B1 deletion in myeloid neoplasms causes nuclear anomaly and altered hematopoietic stem cell function