In approximately 15% of cases, patients with Bone Marrow Failure Syndromes progress to develop the related conditions of Acute Myeloid Leukaemia (AML), Myelodysplastic Syndrome (MDS) or Paroxysmal Nocturnal Haemoglobinuria (PNH). The relationship of these conditions is via their shared root cause of abnormal bone marrow biology, which leads to the suppression of normal bone marrow productivity and/or the emergence of abnormal bone marrow stem cells with cancerous patterns of growth, the hallmark of AML and MDS.
Acute Myeloid Leukaemia occurs when there is an abnormal and increased production of ‘myeloblasts’. Myeloblasts are bone marrow cells that are responsible for the production of white blood cells. Abnormal cells crowd the bone marrow and prevent it from working properly.
Myelodysplastic Syndromes are a group of disorders whereby the bone marrow blood forming stem cells (known as the haematopoietic stem cells) are abnormal and do not function properly. These abnormal stem cells, called blast cells, produce immature red blood cells, white blood cells and platelets that are unable to perform effectively. As such patients suffer from anaemia, susceptibility to infections and bleeding disorders
Paroxysmal Nocturnal Haemoglobinuria is characterised by the body’s abnormal destruction of red blood cells. When the red blood cells are broken apart in a process called haemolysis, the haemoglobin inside the cells (which is the component responsible for carrying oxygen around the body) is released. This causes many of the symptoms of PNH, including haemoglobinuria – haemoglobin in the urine.
PNH occurs as a result of a genetic mutation in a particular gene, the PIG-A gene. As the cell that first acquires the genetic mutation continues to replicate, the number of cells containing the mutation expands.