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As acquisition of the JAK2 V6�7F is considered to �e restricted to myeloid malignancies� the recurrent identification of this mutation in non-small cell lung cancer �NSCLC� merits discussion� particularly in the light of accumulating evidence which suggests that the JAK2 V6�7F may not �e a true driver mutation of NSCLC.

LETTER TO EDITOR

Acute myeloid leukaemia (AML) with 3q26 cytogenetic abnormalities is associated with overexpression of EVI1, dysmegakaryopoiesis and poor prognosis. Screening for EVI1 transcripts was performed in 336 cases of AML, including 139 patients with acute promyelocytic leukaemia (APL). Expression was detected in 7 out of 10 cases with and 23 out of 326 without 3q26 abnormalities including one APL case. Among cases lacking 3q abnormalities, detection of EVI1 transcripts was neither associated with characteristic dysmegakaryopoietic features, nor predictive of a poor outcome, indicating that screening will probably not assist in treatment stratification. This study nevertheless demonstrates that deregulation of EVI1, although rare in APL, is a relatively frequent event in AML.

Hairy cell leukaemia (HCL) has distinct clinical, morphological and immunophenotypic features with no recurrent cytogenetic or molecular abnormalities reported until the recent description of the BRAF V600E mutation in patients with classical HCL. The incidence of this mutation was sought in 27 patients with either classical HCL or HCL variant by an allele-specific PCR approach and findings related to morphology, cytochemistry and immunophenotype. A high degree of correlation was noted between the presence of BRAF V600E and established diagnostic criteria in 26/27 patients with HCL/HCL variant. Detection of the BRAF V600E mutation is therefore a useful adjunct in the differential diagnosis of HCL and HCL variant and highlights the value of a multifaceted approach to the diagnosis of this malignancy.

Acute myeloid leukaemia (AML) with 3q26 cytogenetic abnormalities is associated with overexpression of EVI1, dysmegakaryopoiesis and poor prognosis. Screening for EVI1 transcripts was performed in 336 cases of AML, including 139 patients with acute promyelocytic leukaemia (APL). Expression was detected in 7 out of 10 cases with and 23 out of 326 without 3q26 abnormalities including one APL case. Among cases lacking 3q abnormalities, detection of EVI1 transcripts was neither associated with characteristic dysmegakaryopoietic features, nor predictive of a poor outcome, indicating that screening will probably not assist in treatment stratification. This study nevertheless demonstrates that deregulation of EVI1, although rare in APL, is a relatively frequent event in AML.

Acute myeloid leukaemia (AML) patients with either a t(15;17), t(8;21) or inv(16) at diagnosis have 'good-risk' disease with a favourable response to therapy and improved survival. Detection of cryptic fusion genes created by these translocations has been reported where there is no cytogenetic evidence of the corresponding abnormality. It is likely that these cases share the same favourable prognosis. Secondary cytogenetic changes commonly associated with these rearrangements are +8 with t(15;17), del(9q) with t(8;21) and +22 with inv(16). These secondary abnormalities are also observed alone, raising the possibility that they may be markers of underlying cryptic rearrangements. In order to determine the frequency of these rearrangements in AML cases with +8, del(9q) or +22 we have performed an analysis of 63 such patients in whom there was no evidence of a t(15;17), t(8;21) or inv(16) by cytogenetics. No disease-related fusion transcripts were identified, indicating that the secondary changes are rarely markers for cryptic rearrangements.

Acute myeloid leukaemia (AML) may not only occur as a de novo disease but may evolve from a preceding myelodysplastic syndrome (MDS) or may result from therapy for a previous malignancy. These secondary acute myeloid leukaemias (sAML) possess some common biological and clinical features of the corresponding de novo disorders. The cytokine interleukin-1 (IL-1) is known to have a role in haematopoiesis, and modulation of its action might contribute to the deregulation of proliferation seen in leukaemia. It has recently been reported that a variable number tandem repeat (VNTR) polymorphism in the IL-1 receptor antagonist (IL-1ra) gene is closely associated with the severity of many inflammatory and autoimmune diseases, and may also play a role in the pathogenesis of sAML. We sought to confirm this finding in a large group of patients classified as having sAML. We found no differences in either the genotypic or allele frequencies of the polymorphism studied when compared with those of normal controls or other haematological disorders. No differences were observed in allele frequencies between younger and older patients, or between those patients who had an antecedent myelodysplasia and those who had received prior chemotherapy or radiotherapy. We conclude that the described polymorphism in the IL-1ra gene is not associated with the development of sAML.

Acute myeloid leukaemia (AML) with the t(8;21)(q22;q22) is deemed to be a 'good-risk' disease. 396 patients with AML at diagnosis were screened for the presence of t(8;21) and AML1/ETO fusion transcripts by cytogenetic and RT-PCR techniques respectively. 32 cases of t(8;21) were detected, all of which were also PCR positive. A further 19 cases were detected at the molecular level, predominantly but not exclusively in M1 and M2 FAB types. Approximately 12% of all new cases of AML are estimated to have AML1/ETO fusion transcripts and it is suggested that molecular screening should be performed in all cases with the possible exception of the M3 FAB type.

It has been established that cytogenetic findings at diagnosis of acute myeloid leukaemia (AML) are a powerful prognostic indicator. Patients who have the inv(16)(p13q22), closely associated with the FAB subtype M4Eo. are deemed to have good-risk disease. This subtle translocation may be difficult to detect in poor-quality metaphase preparations and if missed could lead to the incorrect assignment of risk group and influence further treatment strategies. We studied 321 patients with AML at diagnosis for the presence of inv(16)(p13q22) and CBF beta/MYH11 fusion transcripts by cytogenetic and RT-PCR techniques respectively. Karyotypic analysis detected 21 cases of inv(16) (p13q22), all of which were PCR positive. A further 12 cases were detected at the molecular level only, in FAB types other than M4Eo. The observed frequencies of CBF beta/MYH11 fusion transcripts in our study have been adjusted for the reported incidence of each FAB subtype and we calculate that 10.1% of all new cases of AMLs have molecular evidence of inv(16)(p13q22). only half of which are of the M4Eo subtype. We conclude that molecular screening for the presence of CBF beta/MYH11 fusion transcripts should be mandatory in all case of AML at diagnosis.