ALL Case study

What does ALL stand for?

Acute Lymphocytic Leukemia

• most common malignant cancer in children

• symptoms : bruising, night sweat, fevers, rash, sick from infections

• Unknown cause ( some associated with inherited genetic syndromes)

What causes ALL?

• uncontrolled growth of an immature lymphocyte ( a type of white blood cell, or leukocyte)

• these cells are stuck in an early stage of development, become so numerous that they crowd out normal blood cells

Thiopurine drugs

• known to be effective in treating leukemia

• very similar to regular purine nitrogen bases such as adenine and guanine but they have an extra sulfur group attached to them

• They are similar enough that our cells convert them to nucleotides ( with the addition of a deoxyribose sugar and phosphate

• These modified thioguanine nucleotides are then converted into DNA

thioguanine nucleotides (TGN)

• interfere with DNA replication and stop rapidly growing cell like cancer cells from further growth

• Unfortunately, they also block the growth of other fast growing cell needed for good health like the cells in the bone marrow that develop into erythrocytes (red blood cells) and leukocytes

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Enzyme Activity

• the drug can either be converted to the active form, TGN nucleotides

• or, it can be inactivated with the help of TPMT enzyme (thiopurine methyltransferase and then cleared from the body. Caucasian patients were more likely to contain high levels of the enzyme TPMT

• In people with low levels of TPMT, they wouldn’t be able to clear the drug from their body so it would continue to block cell growth

Myelosuppression

deadly condition when the thiopurine drug level are too high

TPMT

• thiopurine methyltransferace

• 34kb with 10 exons

• P arm of chromosome 6

• TPMT is the most common variant

• may be as many as 6 variants - 3 discussed

• three levels of activity- low/ medium/ high