Together with folate, cobalamins are essential cofactors required for DNA synthesis in cells where chromosomal replication and division are occurring—most notably the bone marrow and myeloid cells. As a cofactor, cobalamins are essential for two cellular reactions:

the mitochondrial methylmalonyl-CoA mutase conversion of methylmalonic acid (MMA) to succinate, which links lipid and carbohydrate metabolism, and
the activation of methionine synthase, which is the rate-limiting step in the synthesis of methionine from homocysteine and 5-methyltetrahydrofolate.Cobalamins are characterized by a porphyrin-like corrin nucleus that contains a single cobalt atom bound to a benzimidazolyl nucleotide and a variable residue (R) group. The variable R group gives rise to the four most commonly known cobalamins: CNCbl, methylcobalamin, 5-deoxyadenosylcobalamin, and OHCbl. In the serum, hydroxocobalamin and cyanocobalamin are believed to function as storage or transport forms of the molecule, whereas methylcobalamin and 5-deoxyadenosylcobalamin are the active forms of the coenzyme required for cell growth and replication. Cyanocobalamin is usually converted to hydroxocobalamin in the serum, whereas hydroxocobalamin is converted to either methylcobalamin or 5-deoxyadenosyl cobalamin. Cobalamins circulate bound to serum proteins called transcobalamins (TC) and haptocorrins. Hydroxocobalamin has a higher affinity to the TC II transport protein than cyanocobalamin, or 5-deoxyadenosylcobalamin. From a biochemical point of view, two essential enzymatic reactions require vitamin B12 (cobalamin).Intracellular vitamin B12 is maintained in two active coenzymes, methylcobalamin and 5-deoxyadenosylcobalamin. In the face of vitamin B12 deficiency, conversion of methylmalonyl-CoA to succinyl-CoA cannot take place, which results in accumulation of methylmalonyl-CoA and aberrant fatty acid synthesis.
In contrast, the CdATP:5-NT ratio is relatively low in other cell types, thus sparing numerous non-hematologic cells.In multiple sclerosis, cladribines effectiveness may be due to depletion of B cells, in particular memory B cells. In the pivotal phase 3 clinical trial of oral cladribine in multiple sclerosis, CLARITY, cladribine selectively depleted 80% of peripheral B cells, compared to only 40–45% of CD4+ T cells and 15‒30% CD8+ T cells. More recently, cladribine has been shown to induce long term, selective suppression of certain subtypes of B cells, especially memory B cells.Although cladribine is selective for B cells, the long-term suppression of memory B cells, which may contribute to its effect in multiple sclerosis, is not explained by gene or protein expression. Instead, cladribine appears to deplete the entire B cell department, but while naïve B cells rapidly move from lymphoid organs, the memory B cell pool repopulates slowly from the bone marrow. Both hairy cell leukemia and B-cell chronic lymphocytic leukaemia are types of B cell blood cancers. History in hairy cell leukemia
Ernest Beutler and Dennis A. Carson had studied adenosine deaminase deficiency and recognised that because the lack of adenosine deaminase led to the destruction of B cell lymphocytes, a drug designed to inhibit adenosine deaminase might be useful in lymphomas. Carson then synthesised cladribine, and through clinical research at Scripps starting in the 1980s, Beutler tested it as intravenous infusion and found it was especially useful to treat hairy cell leukemia.