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The Discovery of the MAL Blood Group System: A New Milestone in Medical Science

Blood groups are fundamental to understanding how blood transfusions work, yet they are far more complex than many realize. The two most well-known blood group systems, ABO and Rh, form the foundation of blood typing, yet there are many more, each contributing unique attributes to human biology. For decades, researchers have recognized that blood types extend far beyond these two systems, identifying a total of 47 blood group systems, containing over 360 distinct antigens. However, despite this extensive knowledge, a new blood group system, called MAL, has recently been discovered, adding to the vast and intricate landscape of blood science.


Understanding Blood Groups

Blood groups are defined by the presence or absence of antigens—substances that trigger immune responses—on the surface of red blood cells. In the ABO system, for instance, individuals with type A blood have A antigens, those with type B have B antigens, individuals with AB blood have both, and those with type O blood have neither. The Rh system, another significant blood group system, is determined by the presence or absence of the Rh antigen (often called the Rh factor), which can cause complications during pregnancy and blood transfusions if mismatched.


However, beyond ABO and Rh, blood groups become more intricate. With the discovery of the MAL blood group system, medical science is entering a new phase of understanding, especially in rare and complex cases where patients present with unusual blood characteristics that may not fit neatly within known systems.


The AnWj Antigen and MAL Blood Group System


The AnWj antigen was discovered in 1972, but for over 50 years, its genetic background remained a mystery. Now, after decades of research, scientists led by NHS Blood and Transplant have successfully classified AnWj as part of the newly established MAL blood group system. The discovery of this new system sheds light on rare blood types and promises to improve treatments for individuals who lack this antigen.


AnWj is carried by the Mal protein, found on the red blood cells of over 99.9% of people, meaning they are AnWj-positive. However, in rare cases, individuals may be AnWj-negative, a condition that has significant implications for blood transfusions. If a person who is AnWj-negative receives AnWj-positive blood, they could experience a transfusion reaction, making this discovery highly relevant for managing blood donations and transfusions for these rare individuals.


The Genetic Background of MAL

What makes the MAL blood group system so noteworthy is its genetic foundation. The researchers discovered that individuals who are AnWj-negative inherited this trait due to deletions in the MAL gene, which encodes the Mal protein. In the study, the scientists identified five genetically AnWj-negative individuals, including a family of Arab-Israeli descent, and were able to trace the rare AnWj-negative phenotype back to specific genetic mutations.


Through the use of advanced genetic techniques, including whole exome sequencing (a method for sequencing all the protein-coding genes in a genome), the researchers confirmed that the Mal protein was responsible for carrying the AnWj antigen. By introducing the normal MAL gene into cells and observing the reactivity of AnWj antibodies, they provided definitive proof that the Mal protein is the key to this blood group system.


Implications for Blood Transfusions

One of the most critical applications of this discovery is its potential to improve blood transfusions. For people with the rare AnWj-negative phenotype, receiving AnWj-positive blood can cause dangerous transfusion reactions. Thanks to this research, new genotyping tests can be developed to identify AnWj-negative individuals before transfusions, reducing the risk of complications and ensuring these patients receive safe, compatible blood.


While most cases of AnWj-negativity are associated with hematological disorders or cancer, where antigen expression is suppressed, a small number of individuals inherit this trait genetically. By pinpointing the genetic cause, the discovery of the MAL system will help doctors and transfusion services better identify and treat these rare patients.


A Long Journey to Discovery

This breakthrough represents the culmination of decades of work. Dr. Louise Tilley, who has spent nearly 20 years researching the AnWj antigen, described the discovery as a major achievement. The effort to resolve the genetic mystery of the AnWj antigen has been a long and challenging process, requiring multiple lines of investigation. Dr. Nicole Thornton, another key member of the research team, emphasized the immense effort involved in proving that a gene encodes a blood group antigen. Despite the challenges, the team remained passionate about solving this puzzle, driven by the potential to make a significant difference in the lives of rare patients around the world.


The Future of Blood Group Research

With the establishment of the MAL blood group system, researchers can now develop new genotyping platforms that include tests for the MAL gene. This will allow blood banks and transfusion centers to better identify rare blood types and match donors with patients more precisely. Additionally, the discovery of MAL opens the door to further exploration into the complexities of blood group systems, which may lead to more breakthroughs in the future.


In conclusion, the discovery of the MAL blood group system is a milestone in medical science, offering new insights into the intricate world of blood types. This finding not only resolves a decades-old mystery but also promises to improve the care and treatment of rare patients who lack the AnWj antigen. As blood group research continues to evolve, the discovery of MAL represents another step forward in understanding the complexity of human biology and ensuring safer medical treatments for all.


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References

- Tilley, L. A. et al., 2024. Deletions in the MAL gene result in loss of Mal protein, defining the rare inherited AnWj-negative blood group phenotype. *Blood* 025099; doi: 10.1182/blood.2024025099

- Sci.News - [New Blood Group System Discovered: MAL](https://www.sci.news/biology/new-blood-group-system-mal-11346.html)

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