Once inside a cell, cladribine undergoes phosphorylation by the enzyme deoxycytidine kinase (DCK) to produce mononucleotide 2-chlorodeoxyadenosine 5’monophosphate (2-CdAMP), which is subsequently phosphorylated to the triphosphorylated active compound, 2-chlorodeoxyadenosine 5’triphosphate (2-CdATP).Activated cladribine is incorporated into the DNA synthesis pathway, where it disrupts DNA repair and synthesis, resulting in an accumulation of DNA strand breaks This is followed by the activation of transcription factor p53, the release of cytochrome c from mitochondria and eventual programmed cell death (apoptosis). This process occurs over approximately 2 months, with a peak level of cell depletion 4–8 weeks after treatment.Another family of enzymes, the 5-nucleotidase (5-NT) family, is also capable of dephosphorylating cladribine, making it inactive. The most important subtypes of this group appear to be cytosolic 5-NT, c-5NCT1A and c-NT1B, which are cytosolically active and specific for purine analogues.Accumulation of cladribine into cells is dependent on the ratio of 2-CdATP and 5-NT. This ratio differs between cell types, with high levels in T and B lymphocytes, making them particularly susceptible to cell death. The cells with the highest ratios are B cells, especially germinal centre and naïve B cells. This helps to explain which B cells are more vulnerable to cladribine-mediated apoptosis. DCK is the rate-limiting enzyme for conversion of the cladribine prodrug into its active triphosphate form, leading to the selective depletion of dividing and non-dividing T and B lymphocytes.
Six or more spots of at least 5mm in diameter in pre-pubertal children and at least 15mm in post-pubertal individuals is one of the major diagnostic criteria for NF1. Prognosis
Café au lait spots are usually present at birth, permanent, and may grow in size or increase in number over time.Cafe au lait spots are themselves benign and do not cause any illness or problems. However, they may be associated with syndromes such as Neurofibromatosis Type 1 and McCune-Albright syndrome.The size and shape of the spots can vary in terms of description. In Neurofibromatosis Type 1, the spots tend to be described as ovoid, with smooth borders. In other disorders, the spots can be less ovoid, with jagged borders. In Neurofibromatosis Type 1, the spots tend to resemble the "coast of California," rather than the "coast of Maine," meaning the edges are smoother and more linear. Treatment
Café au lait spots can be removed with lasers. Results are variable as the spots are often not completely removed or can come back after treatment. Often, a test spot is treated first to help predict the likelihood of treatment success. See also
Birthmark
Nevus
List of cutaneous conditions
List of conditions associated with café au lait macules

References
External links

eMedicine