Which cytogenetic analysis findings are characteristic of unclassifiable myelodysplastic syndromes (MDS-U)?

Updated: Jul 21, 2020
  • Author: Robert P Hasserjian, MD; Chief Editor: Christine G Roth, MD  more...
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Cytopenic patients lacking excess blasts or sufficient dysplasia in any lineage may be diagnosed with MDS-U if any of certain cytogenetic abnormalities is detected on bone marrow karyotype. The following abnormalities are considered diagnostic of MDS-U in such a situation [9] : -7, del(7q), -5, del(5q), i(17q), t(17p), -13, del(13q), del(11q), del(12p) or t(12p), del(9q), idic(X)(q13), t(11;16)(q23;p13.3), t(3;21)(q26;q22.1), t(1;3)(p36.3;q21.2), t(2;11)(p21;q23), inv(3)(q21q26.2), t(6;9)(p23;q34). However, many of these cytogenetic abnormalities can also be present in myeloproliferative neoplasm (MPN) and myelodysplastic/myeloproliferative overlap neoplasm (MDS/MPN) entities.

The following image is an example of a cytogenetic analysis.

Pathology of unclassifiable myelodysplastic syndro Pathology of unclassifiable myelodysplastic syndromes (MDS-U). Cytogenetic analysis from a patient with myelodysplastic syndrome, unclassifiable (MDS-U), showing an abnormal 45, XX, -7 karyotype in 15 of 20 metaphases. In a patient with unexplained cytopenia, this finding confirms a diagnosis of MDS-U even in the absence of significant dysplasia in any lineage.

When considering a diagnosis of MDS-U based solely on a cytogenetic finding, other myeloid neoplasms must be carefully excluded by close examination of clinical data, such as the presence or absence of splenomegaly and a complete blood cell (CBC) count and differentials. JAK2 mutation analysis may also be helpful, because although JAK2 mutation is rare in MDS, it is relatively common in MPN and in some types of MDS/MPN. [12, 13] If the abnormality is present in all metaphases, a constitutional abnormality that may not be related to the cytopenia(s) should be considered.


Note that some abnormalities that are frequently observed in MDS cases, +8, -Y, and del(20q), are not considered diagnostic of MDS if these represent sole abnormalities; these cytogenetic abnormalities have been identified in patients with immune disorders and may not necessarily indicate a clonal stem cell abnormality. [14, 15]  Aplastic anemia (AA) and immune thrombocytopenic purpura (ITP) are presumed to be immune-mediated processes that can exhibit cytogenetic abnormalities: trisomies of chromosome 6, 8, and 15; loss of the Y chromosome; as well as monosomy of chromosome 7 have been reported in aplastic anemia, and deletion of the long arm of chromosome 20 has been reported in ITP. [15, 16] Partly for these reasons, +8 and del(20q) abnormalities alone are considered insufficient to make a diagnosis of MDS-U.

However, the significance of a -7 abnormality (that is MDS-defining) in a hypoplastic marrow is less certain. Although some studies suggest that this abnormality confers a poor prognosis and lack of responsiveness to immunosuppression, supporting classification as MDS-U, some cases may still respond to immunosuppression, resembling aplastic anemia. [14, 17] Moreover, some cases of bona fide MDS respond to immunosuppression. [18]

Further study is needed to determine how best to classify and treat cases of hypoplastic marrow with cytogenetic abnormalities; these cases challenge our conceptualization of the distinction between MDS and aplastic anemia.

One particular scenario in which caution must be exercised is in patients with chronic myelogenous leukemia (CML) treated with tyrosine-kinase inhibitors (TKI). Such patients may develop cytogenetic abnormalities, including some that are considered MDS-defining, in remission from CML. Although these cases occasionally progress to MDS and acute myeloid leukemia (AML), in most instances they are transient. Thus, MDS-U should not be diagnosed if a cytogenetic abnormality develops on TKI therapy in the absence of significant dysplasia or increased blasts. [19]

A study by Wang et al found that the WHO 2008 criteria for atypical chronic myeloid leukemia (aCML) identify a subgroup of patients with features clearly distinct from unclassifiable myelodysplastic/myeloproliferative neoplasm. [20]

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