BIOLOGY 2F03 Chapter Notes - Chapter 9-11: Myeloid Sarcoma, Myeloproliferative Neoplasm, Myelofibrosis
20 May 2018
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WHO classification of AML
Therapy-related AML has a worse prognosis which is why it is classified separately.
• alkylating agents cause worse AML – they are associated with abnormalities in c7, c5, inv(3), t
(3;3), (6;9) and (8;16)
• topoisomerase inhibitors cause balanced translocations and account for ~10% of APML. this is
on the up as treatment of other cancers is improving so that survival is long enough to
experience an AML.
• importantly, mutations caused by therapy have a worse prognosis than if the same mutation
occurred de novo.
The next step in the WHO classification is classifying recurrent genetic abnormalities seen in AML,
because they correlate closely to prognosis
The important ones are:
• t(8;21) (q22;q22) [RUNX/RUNX1T1]
o good prognosis
• APML - t(15;17) (q22; q21) [PML/RARA]
o variant M3 is very (but not 100%) similar to true M3 on a genetic and clinical basis. it is
variat eause of orphologial differees – granules cannot be seen on LM but
they can on EM
o the diagnosis between classic and variant M3 lies with using a fluorescent Ab against
PML, which appears microparticulate in variant M3
o survival rates plummet initially because of DIC
o RARA is involved in a number of leukaemias
• inv (16) (p13.1q22) or t(16;16) (p13;q22) [CBFB/MYH11]
o eosinophilia and increased basophil granules
o good prognosis
Some others are:
• t(9;11) (p22;q23) [MLLT3/MLL] – bad prognosis
• t(6;9) (p23;q23) [DEK/NUP214]
• inv (3) (q21q26.2) or t(3;3) (q21;q26.2) [RPN1/EVI1]
• t (1;22) (p13;q13) [RBM15-MKL1]
• NPM1/ CEBPA mutations, these tend to have a good prognosis.
There are many subtypes of AML that can not be classified on a genetic basis
• some of these can be classified morphologically by the FAB system M0-M7
• the others can not:
o transient myeloproliferative disorder in Downs Syndrome
o Acute basophilic leukaemia
o acute panmyelosis with myelofibrosis
o myeloid sarcoma
Summary – roles of cytogenetics in haematological neoplasms
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