TESTS AVAILABLE: Karyotyping and FISH
Precursor B-lymphoblastic leukaemia/lymphoma (pre B-ALL)- t(9;22)(q34;q11.2) BCR/ABL Dual Fusion 9q34/22q11 Translocation Probe;
t(12;21)(p13;q22) ETV6 (TEL)/RUNX1(AML1) ES Dual Colour Translocation Probe; 11q23 rearrangement MLL Dual Colour, Break Apart Rearrangement Probe; Ploidy- CEP 4/CEP10/CEP17 Tricolour Probe, TCF3(19p13) Dual Colour, Break Apart Rearrangement Probe
Precursor T-lymphoblastic leukaemia/lymphoma (pre T-ALL)- 9q34 amplification (NUP214-ABL1); 9p21 gene deletion BCR/ABL Dual Fusion 9q34/22q11 Translocation Probe; P16 (9p21) Spectrum Orange/ CEP 9 Spectrum Green Probe
Mature T-cell Neoplasms (T-ALL)- 14q11 rearrangement TCR alpha/delta Dual Colour Break apart Rearrangement Probe.
Rapid FISH for t(9;22) BCR/ABL1 on direct cultures within 1 working day.
Acute Lymphoblastic leukaemia is a neoplastic disorder that results in the accumulation of lymphocytes in the bone marrow. It can be subdivided according to the level of maturity of the lymphocytes seen and the WHO classification is based on immunophenotyping. There are three main types identifiable: Precursor B-ALL, (a) B-ALL with t(9;22)(q34;q11.2) BCR/ABL1. In both children and adults, t(9;22) has the worst prognosis among patients with ALL. (b) B-ALL with t(v;11q23), MLL rearrangement. This is the most common rearrangement in infants less than one year. The MLL gene has many fusion partners, most commonly AF4 on 4q21 which has a poor prognosis. Other MLL rearrangements can be classified as intermediate but this is controversial. (c) B-ALL with t(12;21)(p13;q22), ETV6-RUNX1. This is most common rearrangement in childhood ALL. It is very rare in adults. It has a favourable prognosis especially if combined with favourable clinical factors. (d) B-ALL with hyperdiploidy. This usually occurs without structural abnormalities. Extra copies are non-random with X, 14, 21 and 4 being most common and chromosomes 1, 2 and 3 being the least common seen. Trisomies of 4, 10 and 17 appear to be the most favourable. It has a favourable prognosis overall but other adverse factors such as age or very high WCC need to be taken into account. (e) B-ALL with hypodiploidy. All patients show loss of one or more chromosomes and can range to haploidy. It is associated with a poor prognosis but those with 44-45 chromosomes have a better outcome. (f) B-ALL with t(1;19)(q23;p13.3) E2A-PBX1. The functional fusion gene resides on chromosome 19 and there may be loss of the derivative 1 resulting in an unbalanced translocation. Rare variants are the t(17;19)( HLF-E2A) which is associated with a dismal prognosis. E2a-PBX1 is now associated with a prognosis between intermediate and poor. Caution needs to be exerted as there is a t(1;19) which can be seen which does NOT involve E2A-PBX1 and so FISH studies should always be carried out to ensure E2A rearrangement. In addition to the abnormalities mentioned above a complex karyotype, and near triploid are also associated with a poor prognosis. Precursor T-ALL, T-ALL almost always shows rearrangement of TCR genes loci at 14q11, 7q35 and 7p14-15. Most translocations involving these genes, involve HOX11(10q24) andHOX11L2 (5q35). Some rearrangements can only be detected molecularly e.g. TALI and SIL rearrangement other rearrangements include t(10;11)(p12q14) CALM-AF10 and deletion of 9p(CDKN2A). T-ALL adult patients in general has an intermediate prognosis but in childhood has a poor prognosis. Burkittst(8;14)(q22;q32) and variants IGH/MYC, Biphenotypic acute leukaemia (Acute leukaemia of ambiguous lineage). Most cases have clonal cytogenetic abnormalities but nothing specific. Can be found abnormalities of 5, 6, and 7 and near tetraploidy.