Cytogenetics are now routinely recommended for myelofibrosis. Guidelines (Reilly et al) indicate that beyond a routine bone marrow aspiration and biopsy, JAK2 V617F mutation screening should be carried out routinely in patients with primary myelofibrosis (PMF). Quantitative results are not required for clinical management.BCR-ABL1 rearrangement should be excluded in cases with atypical trephine biopsy features, or if the patient lacks a mutation in JAK2 or MPL. PDGFRA and PDGFB rearrangements should be excluded in the presence of significant eosinophilia. (Screening for other mutations remains a research tool and routine screening cannot be justified, apart from in cases of diagnostic difficulty where detection of a clonal abnormality would be informative) (Evidence level 2, Grade B). This recommendation does not include cytogenetics.
Recently there is evidence that cytogenetics can refine prognostic information which can help make decision, especially about stem cell transplantation. The factors not included in the IPSS that affect survival are represented by red cell transfusion need,12 thrombocytopenia,13 and “unfavorable” karyotype. Regarding the latter, patients with unfavorable karyotype, which includes a complex karyotype or sole or 2 abnormalities such as +8, −7/7q−, i(17q), inv(3), −5/5q−, 12p−, or 11q23, had a median survival of 2 years compared with 5.2 years for those with a “favorable” karyotype, defined as no abnormality or any other apart from those included in the above category, the 5-year survival rates were 8% and 51%, respectively. The newly devised DIPSS Plus score11 incorporates these additional 3 variables for improved prognostic categorization. In a series of 793 patients, median survival times were 185, 78, 35, and 16 months for the low, intermediate-1, intermediate-2, and high-risk categories, respectively.
Based on its inclusion into a recommended prognostic tool DIPSS Plus, cytogenetics should not longer be considered investigational
Reilly JT, McMullin MF, Beer PA, Butt N, Conneally E, Duncombe A, Green AR, George Michaeel N, Gilleece MH, Hall GW, Knapper S, Mead A, Mesa RA, Sekhar M, Wilkins B, Harrison CN, Writing group: British Committee for Standards in Haematology. Guideline for the diagnosis and management of myelofibrosis. Br J Haematol. 2012 Aug;158(4):453-71. [123 references]
Jennifer Dunlap, MD, Katalin Kelemen, MD, PhD, Nicky Leeborg, MD, Rita Braziel, MD, Susan Olson, PhD, Richard Press, MD, PhD, James Huang, MD, Ken Gatter, JD, MD, Marc Loriaux, MD, PhD, Guang Fan, Association of JAK2 Mutation Status and Cytogenetic Abnormalities in Myeloproliferative Neoplasms and Myelodysplastic/Myeloproliferative Neoplasms Am J Clin Pathol. 2011;135(5):709-719.