Successful blood stem cell transplant gives cancer patients second chance

Did you know that in India, every 5 minutes someone is diagnosed with a blood cancer or blood disorder? And that for most people a blood stem cell donation from a stranger with similar tissue type is their best – or only – chance of survival?

Blood cancer refers to the defects in the blood-forming system which starts in the bone marrow. This leads to the formation of immature or dysfunctional blood cells that multiply uncontrollably, crowding out the healthy cell.  Blood cancer is also one of the most common cancers reported in India.

Many blood cancer patients are children and young people whose chance of recovery from blood cancer is a successful blood stem cell transplant donated from a matching donor. For an individual to be able to donate their blood stem cells a match in HLA / tissue type is important.

HLA is the abbreviation of ‘human leucocyte antigen’ which is commonly known as ‘tissue types’. The HLA or Human leucocyte antigen is our body’s way of distinguishing between its own and alien tissue. Though tissue types are passed from parents to their children, only about 30% of the patients in need of a stem cell transplant as a life-saving treatment, can find a sibling match. The rest 70% depend on finding a matching unrelated donor. That’s when a registry is looked up to. A stem cell registry is typically a database of potential donors.

Anannya, an 8-year-old kid in Mumbai, was diagnosed with a relapse of Acute Lymphoblastic Leukemia (ALL), a type of blood cancer common in children. While Anannya is currently undergoing chemotherapy, she needs a perfect matching donor to undergo a stem cell transplant, which is her only hope of survival.

For a successful stem-cell transplant, ethnicity plays a key role in finding the perfect match. Patients and donors of Indian origin have unique HLA characteristics that can be found only among the Indian group. But due to the lack of awareness and myths and facts associated with stem cell donation there is an under-representation of Indians in the stem cell registry. This makes it extremely difficult for Indian patients to find a matching unrelated donor. Hence with the consistent increase in the disease burden in India, the need for increasing the Indian representation in a stem-cell registry has now become a priority.  

To address this need gap, it is important for people to be aware of the do’s and don’ts of stem-cell donation and how one can become a potential donor. It is also important for people to realize that blood cancer is not the end and a patient can recover if provided with blood stem cells from a matching donor.

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Glucose not responsible for inflammation in type 2 diabetes

To date, the underlying causes of inflammation in obesity and type 2 diabetes mellitus (T2DM) have been poorly understood, but a new research seems to have made a breakthrough by finding that that changes to mitochondria--the powerhouse of cells--drive chronic inflammation from cells exposed to certain types of fats, shattering the prevailing assumption that glucose was the culprit.

According to the study, chronic inflammation fuels many of the devastating complications of type 2 diabetes, including cardiovascular, kidney, periodontal diseases, and is thus one of the key targets for therapy development.

This new data may enlighten the conversation about tight glycemic control as the dominant treatment goal for people with diabetes.

Research  didn't set out to disprove the glucose-inflammation causation theory.

Based on the importance of glycolysis--a 10-reaction sequence that produces energy--in other types of inflammation, the team hypothesised those immune cells from patients with type 2 diabetes would produce energy by burning glucose. "We were wrong," he said.

"We exclusively used immune cells from human subjects for all of the work," he explained, noting that humans, but not animal models of type 2 diabetes, have the specific pro-inflammatory T cell profile her team had identified in earlier research.

The team was surprised to find that glycolysis wasn't driving chronic inflammation. Instead, a combination of defects in mitochondria and elevated fat derivatives were responsible.

Nikolajczyk said she sees applications for this research in both basic and clinical sciences. She hopes to precisely define pro-inflammatory lipid types and explore associations between circulating and/or tissue-associated lipids and insulin resistance, one key feature of Type 2 diabetes.

She is also interested in contributing to the development of new analytical approaches, spearheaded by Dr. Lauffenburger's team, that leverage ongoing lipid-related findings into a new understanding of pathology in type 2 diabetes.

"Aggressive blood glucose control to lower the risk of diabetic complications has been the goal for most people with Type 2 Diabetes for decades. Our data provide an explanation for why people with tight glucose control can nonetheless have disease progression," Nikolajczyk said.

Family history of diabetes associated with increased bone mineral density

The association between type 2 diabetes and increased fracture risk is well documented. However, little was known about the possible effect of family history of diabetes on bone mineral density (BMD). A study from China now confirms that a history of first-degree family members with diabetes is linked to increased BMD as well as to insulin resistance. Results are published online in Menopause, the journal of The North American Menopause Society (NAMS).

Because patients with type 2 diabetes are at an increased risk of fracture, understanding the early pathophysiology of altered BMD could be critical in the development of preventive strategies for diabetic osteoporosis. Although strong evidence has revealed normal to high BMD in most patients with type 2 diabetes, no data have been published, to date, that demonstrate whether BMD is altered in persons with a first-degree family history of diabetes.

In this new study involving nearly 900 normoglycemic postmenopausal women, it was found that the BMD of the lumbar spine and femoral neck was significantly higher in participants with a first-degree family history of diabetes than in those without such history, even in women with normal blood glucose levels. These same participants additionally showed increased insulin resistance and hyperinsulinemia.

"This study shows an association between a family history of diabetes and increased bone density in postmenopausal women. This finding may be related to higher insulin levels in these women with a hereditary predisposition to diabetes, because insulin has a bone-building effect. Although this sounds like good news, these women are at increased risk for developing diabetes, which is associated with skeletal fragility and increased fracture risk," says Dr. Stephanie Faubion, NAMS medical director.

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Endogamy may up infertility risk in Indian men

A team of researchers have identified that deletions of the Y chromosomes, responsible for production of sperms, can cause infertility in Indian men.

The study, illustrates how the ethnicity, endogamy and long-time geographical isolation of Indian populations might have played a major role in the high frequencies of deletion events.

According to the researchers, deletions in the AZoospermia Factor (AZF) regions on the human Y chromosome are reported as one of the most common causes of severe testiculopathy and spermatogenic defects leading to male infertility.

For the study, the researchers screened blood samples of 973 infertile men, consisting of 771 azoospermia (complete absence of sperm), 105 oligozoospermia (low sperm count) and 97 oligoteratozoospermia (low sperm count with abnormal shape and size) patients.

The deletion screening was carried out using AZF-specific markers.

The experiments were carried in accordance with the relevant guidelines and regulations approved for research on human samples.

The study revealed deletion events in a total of 29.4 per cent of infertile Indian men. Of these, non-allelic homologous recombination events accounted for 25.8 per cent.

Indian populations are unique in their origin and have been practicing endogamy for the last two thousand years, and therefore it is important to add a study of the frequencies of AZF deletions on the Y chromosome and their association with fertility in Indian idiopathic infertile men to similar studies from other parts of the world, the researchers said.

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