Acute Myeloid leukaemia (AML)

AML is s neoplastic disorder that results from a block in the differentiation of haematopoietic progenitor cells along with uncontrolled proliferation. Cytogenetics is one of the most important prognostic factors and WHO classification recognised recurrent cytogenetic abnormities in its revision in 2008. These abnormalities are AML with t(8;21)(q22;q22) RUNX1/RUNX1T1(AML1),AMLwith inv(16)(p13.1q22) or t(16;16)(p13.1:q22) CBFB/MYH11, acute promyelocytic leukaemia with t(15;17)(q22;q12) PML/RARA. All of these abnormalities are associated with a favourable prognosis. AML with t (9; 11) (p22; q23) MLLT3-MLL and a normal karyotype is associated with an intermediate prognosis. AML with t(6;9)(p23;q34) DEK-NUP214, inv(3)(q21q26) or t(3;3)(q21;q26.2) RPN1/EV11, t(9;22)(q34;q11.2), complex karyotype, MLL rearrangement, -5, 5q-, -7, 7q- are all associated with a poor prognosis. In AML the prognostic implications are important as they are used in stratified treatment regimes.For APML the other variant partner of RARA (eg PLZF) is recognised as separate entities as they lack typical morphology and is resistant to ATRA therapy. For all MLL rearrangements that involve partner genes other than MLLT3 should be specified in the diagnosis. In AML with MDS related changes, which in most cases occur in elderly patients, there are certain cytogenetic changes which are sufficient to confirm the diagnosis. This is relevant only in cases which have over 20% blasts. These are -7/del7q, -5/del5q, i(17q),i(17)(p), -13/del13q, del11q, del12p/t(12p),del 9q, and idic(X)(q13). A number of balanced translocations which are associated with both MDS and therapy related AML can be found in the WHO classification tables and include t(3;21)(q26.2q22.1) and t(3;5)(q25;q34).Approximately 40% of new diagnostic AML cases have a normal karyotype but most of these harbour molecular lesions such as FLT3 ITD and NPM1 mutation.