All content on this site is intended for healthcare professionals only. By acknowledging this message and accessing the information on this website you are confirming that you are a Healthcare Professional. If you are a patient or carer, please visit the MPN Advocates Network.

The MPN Hub uses cookies on this website. They help us give you the best online experience. By continuing to use our website without changing your cookie settings, you agree to our use of cookies in accordance with our updated Cookie Policy

Clinico-biological features and prognosis of patients with MDS/MPN-U with isolated isochromosome 17q

Dec 30, 2021

Isochromosome 17q [i(17q)] is a rare, isolated abnormality identified in Philadelphia chromosome-negative myeloid neoplasms that has high rate of transformation to AML.1 It is often characterized by hybrid clinical and morphological myeloproliferative and myelodysplastic features. Using the current World Health Organization (WHO) criteria, many cases are unable to be categorized into one of the specific subtypes of myelodysplastic/myeloproliferative neoplasms (MDS/MPN); in turn, these cases are mostly grouped under the heterogenous category of unclassifiable MDS/MPN (MDS/MPN-U). A combination of a specific molecular profiling and shared clinicopathologic features may be useful to distinguish myelodysplastic/myeloproliferative subtypes.1

Among cases of MDS/MPN-U, those with isolated i(17q) showed similar clinical, pathological, mutational, and cytogenetic features, indicating a common pathobiology. However, there is a shortage of study data justifying the recognition of this condition as a distinct subtype within the category of MDS/MPN-U.

Here, we summarize the key findings by Kanagal-Shamanna et al.,1 published in the journal Modern Pathology, comparing different features within cases of MDS/MPN-U with isolated i(17q) to cases of MDS/MPN-U without i(17q) as well as to other well-characterized MDS/MPN subtype samples, in order to better characterize features of this condition.


All cases of MDS/MPN-U, according to the WHO criteria, from the institutional databases of eight institutions in the United States were studied.

The inclusion criteria for this study group included cases with

  • a 2016 WHO diagnosis of MDS/MPN-U;
  • an adequate karyotype at baseline showing i(17q) as an isolated abnormality or with one additional abnormality other than del(7q)/-7;
  • a negative for BCR/ABL1 rearrangement; and
  • a normal karyotype at baseline that developed isolated i(17q) abnormality over their disease course.

The control group included patients with MDS/MPN-U without an i(17q) abnormality in the baseline karyotype that were diagnosed over the same time period and who did not meet the WHO criteria for chronic monomyelocytic leukemia (CMML), atypical chronic myeloid leukemia (aCML), MDS/MPN with ring sideroblasts and thrombocytosis (MDS/MPN-RS-T), juvenile monomyelocytic leukemia (JMML), or any other myeloid neoplasm.

For the morphological evaluation of cells, core biopsy or clot sections of blood and bone marrow specimens were stained with Wright–Giemsa and hematoxylin-eosin stains. Karyotyping by G-banding was done for cytogenetic evaluation. Fluorescent in-situ hybridization studies were performed for TP53 gene deletion and rearrangement of BCR/ABL, PDGFRA, PDGFRB, or FGFR1. Somatic gene mutations were analyzed using an amplicon-based next-generation sequencing (NGS) panel.


Patient characteristics

A total of 92 adult patients were identified for the study: 29 patients with isolated i(17q) in the study group and 63 patients without an i(17q) abnormality in the control group.

Compared with the control group, the study group was significantly younger, had significantly lower absolute neutrophil counts and median hemoglobin levels, and had a higher frequency of splenomegaly, as well as a trend for higher peripheral blood blast cells (Table 1). In the study group, 90% of patients had sole i(17q) while others had an additional trisomy 13 abnormality; the median clonal burden of i(17q) was 60%.

Table 1. Clinical, peripheral blood, and bone marrow features of patients*


MDS/MPN-U with isolated i(17q)
 = 29)

MDS/MPN-U without i(17q)
 = 63)


Median age, years (range)




Male gender, %




Splenomegaly (frequency), %




PB counts

Hemoglobin, g/dL




White blood cell counts ×109/L (range)




Median platelet count ×109/L (range)




Median ANC ×109/L (range)




PB blasts (median, range)




BM morphologic features

Median BM blasts, % (range)




Dyserythropoiesis, %




Dysgranulopoiesis, %




Dysmegakaryopoiesis, %




Grade 2/3 MF, %




ANC, absolute neutrophil count; BM, bone marrow; MDS, myelodysplastic syndrome; MF myelofibrosis; MPN-U, myeloproliferative neoplasm unclassifiable; NS, not significant; PB, peripheral blood.
*Adapted from Kanagal-Shamanna et al.1
Calculated based on the number of patients with available data.

Bone marrow morphologic features

Using the WHO criterion (at least 10% dysplastic cells), MDS/MPN-U with i(17q) showed a higher frequency of megakaryocytic dysplasia compared with MDS/MPN-U without isolated i(17q) (100% vs 73%; p = 0.008). There was a non-significant increase in median bone marrow blast percentage in the study group compared with the control group (4% vs 2%; p = 0.106) with no differences in granulocytic, erythroid dysplasia, or the degree of bone marrow fibrosis.

When different types of dysplasia were compared, there was a significantly higher frequency of pseudo-Pelger–Hüet neutrophils and a tendency of elevated mono/hypolobated megakaryocytes in the study group when a dysplasia score of 1 was used. Increased pseudo-Pelger–Hüet neutrophils in the study group was observed with a dysplasia score of 3.

Somatic gene mutation analysis

Comprehensive NGS-based mutation data were available for 16 patients in the study group and 21 patients in the control group. The data were collected from multiple gene panels, each specific to the institution, but included most of the genes implicated in myeloid malignancies.

  • The mutations in SETBP1 (69% vs 14%; p = 0.002) and SRSF2 (63% vs 24%; p = 0.023) were more frequent in cases with i(17q) compared with those without i(17q).
  • Double mutations involving SRSF2/SETBP1 were significantly more frequent in MDS/MPN-U with i(17q) (44% vs 5%; p = 0.012), and a similar trend was noted with triple mutations involving SRSF2/SETBP1/ASXL1 (31% vs 5%; p = 0.066).
  • In the study and control groups, the ASXL1 (67% vs 43%, respectively) and TET2 (19% vs 33%, respectively) genes showed considerable mutations, with non-significant differences between them.
  • TP53 mutations were rare, and none of the patients had an MPN driver mutation at a high allele burden.
  • There was no report of MPL mutation.

Comparison of the mutation profile of MDS/MPN-U with isolated i(17q) with other MDS/MPN subtypes

The overall mutation landscape of MDS/MPN-U with i(17q) overlapped with that of aCML and partly with CMML but was significantly different from MDS/MPN-RS-T.

MDS/MPN-U with i(17q) showed

  • a significantly higher frequency of ASXL1 and SRSF2 mutations compared with MDS/MPN-RS-T (p = 0.0022 and p = 0.0009, respectively);
  • a higher frequency of SETBP1 mutations compared with CMML (p < 0.0001); and
  • significantly higher SRSF2/SETBP1 double mutant and SRSF2/SETZBP1/ASXL1 triple mutant combinations when compared with both CMML and MDS/MPN-RS-T (p < 0.0001).

Survival analysis

The follow-up data were available in 28 patients in the study group and in all patients in the control group over a median duration of 52 months.

  • Median overall survival (OS) was significantly shorter in patients with baseline i(17q) compared with those without i(17q) (10.6 vs 27.6 months, respectively; p < 0.001).
    • 82% of patients with i(17q) died.
  • In the univariate analysis of the entire MDS/MPN-U cohort, the presence of i(17q), higher bone marrow and peripheral blood blast percentages, and splenomegaly were associated with a shorter OS.
  • Multivariable analysis confirmed the presence of i(17q) (hazard ratio [HR], 1.69; p = 0.026) and splenomegaly (HR, 6.98; p = 0.001) as independent predictors for shorter OS. Peripheral blood blast percentage became only borderline significant (HR, 1.2; p = 0.073).

When compared with cases harboring SRSF2/SETBP1 double mutations, the frequency of splenomegaly was higher, and the OS was poorer—though the difference was not significant.


This study attempted to provide a comprehensive assessment of clinicopathologic and genomic characteristics of MDS/MPN-U with isolated i(17q) in the largest dataset to the knowledge of the authors. The study demonstrated that unique clinical and morphological features that do not meet WHO criteria for other MDS/MPN subtypes, complex patterns of prognostically adverse mutations, lack of TP53 mutation, and generally poor prognosis warrants the recognition of MDS/MPN-U with i(17q) as a distinct entity within the MDS/MPN-U category. These findings emphasized the urgent need for prospective clinical trials in these patients using uniform therapy.

The authors propose the following criteria for MDS/MPN with isolated i(17q), to help patient enrollment in clinical trials and validation:

  • Myeloid neoplasm with mixed myeloproliferative and myelodysplastic features at onset, failing to meet the WHO criteria for any other MDS/MPN, MDS, or MPN entities;
  • <20% blasts (including myeloblasts, monoblasts, and promonocytes) in the bone marrow and peripheral blood;
  • Concurrent presence of clinical and morphological MDS and MPN features (MPN features defined as a platelet count ≥450 × 109/L with bone marrow megakaryocytic proliferation and/or a white blood cell count of ≥13 × 109/L);
  • Presence of isolated i(17q) or with one additional abnormality except del(7q)/-7;
  • Absence of BCR/ABL1 fusion; absence of PDGFRA, PDGFRB or FGR1 rearrangement; absence of PCM1-JAK2 fusion mutation;
  • Absence of MPN driver mutations (JAK2, CALR, and MPL); and
  • No history of recent cytotoxic or growth factor therapy that could explain MDS/MPN features.

  1. Kanagal-Shamanna R, Orazi A, Hasserjian RP, et al. Myelodysplastic/myeloproliferative neoplasms-unclassifiable with isolated isochromosome 17q represents a distinct clinico-biologic subset: a multi-institutional collaborative study from the Bone Marrow Pathology Group. Mod Pathol. 2021. Online ahead of print. DOI: 10.1038/s41379-021-00961-0