Chromosome 7 deletions are associated with unfavorable prognosis in myelofibrosis with myeloid metaplasia

Several studies suggest a poor prognosis for patients with myelofibrosis (MF) with an abnormal karyotype, but the prognostic impact of specific cytogenetic lesions is difficult to define.¹  Using conventional cytogenetics, Tefferi et al were able to demonstrate that +8 and 12p- were associated with inferior survival in 165 MF patients.²  Notably, abnormal metaphases were obtained in only 48% of patients at diagnosis, most likely due to the low proliferative capacity of MF tumor cells in vitro. Thus, the prevalence of defined chromosomal aberrations is a matter of uncertainty, and correlations of cytogenetic findings to clinical course are hampered by the low number of informative cases. Interphase cytogenetic analysis (fluorescence in situ hybridization [FISH]) can overcome some of these limitations, as suggested by a small study including 42 MF patients.³ 

To obtain further information on the prognostic impact of specific chromosomal aberrations, we have retrospectively studied 107 MF patients from 2 institutions. FISH was performed on deparaffinized bone marrow sections as described previously,⁴  using commercially available probes for chromosomal regions 7q31, 12p, 13q14, 17p13.1, 20q13.2, 21q22, cen7, cen8, cen11, and cen17 (probes used in dual combinations; eg, cen7/7q31). The diagnostic bone marrow paraffin-block was obtained in 96 cases and from a later stage of disease in 11 patients. Cutoff values for FISH were based on 11 patients with lymphoma without bone marrow involvement. The cutoff for loss of signals was mean + 3 × SD of controls (ie, 11.33 + 3 × 5.75 for -cen7 and 11.82 + 3 × 6.17 for 7q31-). The mean number of interphase nuclei analyzed was 89.

There were 53 females and 54 males, with a median age of 68 years (range, 24-87 years). Of the patients, 28 (26%) were 60 years or younger, and 15 (14%) were 50 years or younger. There were 83 patients who had chronic idiopathic MF (CIMF), and 24 had secondary MF (19 postpolycythemic and 5 postthrombocythemic). Median follow-up was 34 months and median survival was 64 months.

Neither the presence of any cytogenetic abnormality (56% of patients) nor the number of abnormalities (35.5% had more than one abnormality) was associated with prognosis.²  Of all defined cytogenetic abnormalities, only -7 and/or 7q- (6.5% of patients) were significantly associated with adverse prognosis in univariate and multivariate analyses including all cytogenetic parameters (Figure 1). In 6 of 7 patients, -7/7q- was associated with other chromosomal aberrations, but the presence of -7/7q- was not correlated with a specific second abnormality. The parameter “-7/7q-” remained prognostically significant in all patients and the subset of CIMF patients when compared with the LILLE score in multivariate analysis.⁵ 

In a recent report focusing on MF patients with leukemic transformation, -7/7q- were present in only 6.3% of patients at diagnosis, but in 19.6% at the time of transformation.⁶  In our series, the presence of -7/7q- did not correlate with leukemic transformation.

Chromosome 7 deletions were reported to be associated with adverse prognosis in acute myeloid leukemia and myelodysplastic syndrome.^7,8  Our findings show an adverse impact in MF and underline the prognostic significance of chromosome 7 deletions in myeloid disorders.