nodes can be prominent features. The B symptoms, such as fever, night sweats, and weight loss, are often present as well. Central nervous system (CNS) symptoms such as cranial neuropathies due to meningeal infiltration are identified in less than 10% of adults and less than 5% of children, particularly mature B-cell ALL (Burkitt leukemia) at presentation. The signs and symptoms of ALL are variable and include: Generalized weakness and feeling tired Anemia Dizziness Headache, vomiting, lethargy, neck stiffness, or cranial nerve palsies (CNS involvement) Frequent or unexplained fever and infection Weight loss and/or loss of appetite Excessive and unexplained bruising Bone pain, joint pain (caused by the spread of "blast" cells to the surface of the bone or into the joint from the marrow cavity) Breathlessness Enlarged lymph nodes, liver, and/or spleen Pitting edema (swelling) in the lower limbs and/or abdomen Petechiae, which are tiny red spots or lines in the skin due to low platelet levels Testicular enlargement Mediastinal mass Cause The cancerous cell in ALL is the lymphoblast. Normal lymphoblasts develop into mature, infection-fighting B-cells or T-cells, also called lymphocytes. Signals in the body control the number of lymphocytes so neither too few nor too many are made. In ALL, both the normal development of some lymphocytes and the control over the number of lymphoid cells become defective. ALL emerges when a single lymphoblast gains many mutations to genes that affect blood cell development and proliferation. In childhood ALL, this process begins at conception with the inheritance of some of these genes. These genes, in turn, increase the risk that more mutations will occur in developing lymphoid cells. Certain genetic syndromes, like Down Syndrome, have the same effect. Environmental risk factors are also needed to help create enough genetic mutations to cause disease. Evidence for the role of the environment is seen in childhood ALL among twins, where only 10–15% of both genetically identical twins get ALL. Since they have the same genes, different environmental exposures explain why one twin gets ALL and the other does not. Infant ALL is a rare variant that occurs in babies less than one year old. KMT2A (formerly MLL) gene rearrangements are most common and occur in the embryo or fetus before birth. These rearrangements result in increased expression of blood cell development genes by promoting gene transcription and through epigenetic changes. In contrast to childhood ALL, environmental factors are not thought