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The inv(3)(q21q26)/t(3;3)(q21;q26) is frequently accompanied by alterations of the RUNX1, KRAS and NRAS and NF1 genes and mediates adverse prognosis both in MDS and in AML: a study in 39 cases of MDS or AML

Leukemia volume 25, pages 874–877 (2011)Cite this article

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In the 2008 WHO (World Health Organization) classification, acute myeloid leukemia (AML) with inv(3)(q21q26)/t(3;3)(q21;q26) represents a distinct entity in the category ‘AML with recurrent genetic abnormalities’1 due to its specific clinical, morphological and genetic profile: cases show increased numbers of dysplastic megakaryocytes often with one or two nuclei, multilineage dysplasia and normal or elevated thrombocytes. Immunophenotypes are characterized by the expression of CD13, CD33, HLA-DR, CD34 and CD38 antigens, and by the aberrant coexpression of CD7, CD41 and CD61 as reported previously.1 Additional cytogenetic abnormalities are common, the most frequent being monosomy 7. inv(3)(q21q26)/t(3;3)(q21;q26) is associated with prognostically adverse upregulation of the EVI1 (ecotropic viral integration site 1 on 3q26.2) proto-oncogene. Juxtaposition of the RPN1 (Ribophorin) gene on 3q21 to EVI1 (on 3q26) was suggested to cause upregulation of EVI1 in inv(3)(q21q26)/t(3;3)(q21;q26) cases. Other cytogenetic subgroups—such as AML with monosomy 7 or 11q23/MLL rearrangements2 or with complex aberrant karyotypes3 also show EVI1 overexpression.

According to WHO, cases with t(8;21)(q22;q22)/RUNX1-RUNX1T1, inv(16)(p13q22)/CBFB-MYH11 or t(15;17)(q22;q12)/PML-RARA are considered acute leukemias irrespective of blast counts. In contrast, according to WHO, cases with inv(3)(q21q26)/t(3;3)(q21;q26) and blasts <20% are categorized as myelodysplastic syndromes (MDSs). Whether this is reasonable has to be evaluated further, and the profiles of associated molecular markers in AML or MDS with inv(3)(q21q26)/t(3;3)(q21;q26) remain to be investigated. To clarify these questions, we analyzed 39 cases of AML (n=23) or MDS (n=16) with an inv(3)(q21q26)/t(3;3)(q21;q26) selected from our database for additional cytomolecular and molecular markers and for the clinical profiles independent of the morphological categories: 20 females and 19 males at a median age of 64.8 years (range, 36.3–91.3). For further comparisons, an additional cohort of 814 de novo AML patients from other cytogenetic subgroups (401 females, 413 males; median age, 62.8 years; range, 17.1–93.3 years) was included in this analysis. Bone marrow samples were sent from different centers to the MLL Munich Leukemia Laboratory in the period August 2005–June 2009. Patients gave consent to use laboratory data for research purposes. The study adhered to the Declaration of Helsinki. All patients included in the de novo AML survival analysis were treated with intensive chemotherapy protocols and were in part included in controlled trials of German study groups.

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Authors and Affiliations

  1. MLL Munich Leukemia Laboratory, Munich, Germany

    C Haferlach, T Haferlach, F Dicker, T Alpermann, W Kern & S Schnittger

  2. Department for Stem Cell Transplantation, University of Hamburg, Hamburg, Germany

    U Bacher

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  1. C Haferlach
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Correspondence to C Haferlach.

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CH, TH, WK and SS declare part ownership of the Munich Leukemia Laboratory. FD and TA are employed by the Munich Leukemia Laboratory. UB declares no conflict of interest.

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Haferlach, C., Bacher, U., Haferlach, T. et al. The inv(3)(q21q26)/t(3;3)(q21;q26) is frequently accompanied by alterations of the RUNX1, KRAS and NRAS and NF1 genes and mediates adverse prognosis both in MDS and in AML: a study in 39 cases of MDS or AML. Leukemia 25, 874–877 (2011). https://doi.org/10.1038/leu.2011.5

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