Scientists Identify New MAL Blood Group After 50 Years

In 1972, doctors took a blood sample from a pregnant woman and found that it lacked a surface molecule present on every other red blood cell known at that point.

Five decades later, this unusual molecular absence enabled researchers in the UK and Israel to define a previously unknown human blood group system. The team published its findings in 2024.

"It represents a huge achievement, and the culmination of a long team effort, to finally establish this new blood group system and be able to offer the best care to rare, but important, patients," UK National Health Service haematologist Louise Tilley said last September, after nearly 20 years of personally researching this bloody quirk.

How the MAL blood group fits alongside ABO and Rh

Although the ABO blood group system and the Rh factor - the plus or minus designation - are widely recognised, people have numerous blood group systems. These are determined by the broad range of proteins and sugars on the surface of blood cells.

Among their other roles, these antigen molecules act as identity labels, allowing the body to distinguish 'self' from potentially harmful foreign cells.

When these markers are incompatible during a blood transfusion, a procedure intended to save a life can instead trigger reactions or even prove fatal.

Most of the major blood groups were identified in the early 20th century. Many systems discovered later, including the Er blood system first reported by researchers in 2022, affect only a small number of people. The newly identified blood group follows the same pattern.

"The work was difficult because the genetic cases are very rare," explained Tilley.

Earlier research showed that more than 99.9 percent of people carry the AnWj antigen, which was absent from the 1972 patient's blood. Because this antigen is found on a myelin and lymphocyte protein, the researchers named the newly defined system the MAL blood group.

The rare AnWj-negative MAL blood type

People with mutated versions of both copies of their MAL genes have an AnWj-negative blood type, as did the pregnant patient. Tilley and her colleagues also identified three patients with this rare blood type who did not have the mutation, indicating that blood disorders can sometimes suppress the antigen.

"MAL is a very small protein with some interesting properties which made it difficult to identify and meant we needed to pursue multiple lines of investigation to accumulate the proof we needed to establish this blood group system," explained University of the West of England cell biologist Tim Satchwell.

After decades of investigation, the team confirmed it had identified the right gene by introducing the normal MAL gene into AnWj-negative blood cells. This caused those cells to display the AnWj antigen.

The MAL protein is known to be essential for maintaining stable cell membranes and supporting cell transport. Previous work also established that newborn babies do not have AnWj, which emerges shortly after birth.

Notably, every AnWj-negative patient included in the study had the same mutation. Yet researchers found no other cell abnormalities or diseases linked to that mutation.

With the genetic markers underlying the MAL mutation now identified, patients can be tested to determine whether their negative MAL blood type is inherited or results from suppression. Suppression may indicate another underlying medical issue.

These uncommon blood variations can have devastating consequences for patients. The more that is understood about them, the more lives may be saved.

The research was published in Blood.

An earlier version of this article was published in September 2024.