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UPD1p indicates the presence of MPL W515L mutation in RARS-T, a mechanism analogous to UPD9p and JAK2 V617F mutation

Leukemia volume 23, pages 610–614 (2009)Cite this article

Refractory anemia with ringed sideroblasts and thrombocytosis (RARS-T) has been considered a provisional subtype within the diagnostic entity of myelodysplastic syndrome/myeloproliferative disorder diseases (MDS/MPD). As JAK2 V617F mutation is present in a significant proportion of RARS-T patients,1 many investigators consider this entity to be more closely related to classical MPD. However, a significant minority of patients with RARS-T do not harbor a JAK2 V617F mutation. These patients may have acquired other mutations described in MPD, such as MPL W515L/K2, 3 or may represent RARS cases with other thrombocytosis-inducing conditions. We have previously described an aberrant STAT5 phosphorylation pattern that may be an indicator of dysregulation in signal-transduction pathways involved in the pathogenesis of MPD.1

In addition to phospho-STAT5 immunohistochemistry, cytogenetics may aid the diagnosis of MPD/MDS diseases. Recently, we have described the application of single-nucleotide polymorphism array (SNP-A)4 as an important tool that can increase the diagnostic value of metaphase cytogenetics (MC) in MDS and MDS/MPD. In particular, SNP-A allows detection of uniparental disomy (UPD), a mechanism for obtaining loss of heterozygosity (LOH) that can affect multiple chromosomes noted to be remarkably frequent in MDS/MPD patients.4 UPD9p is an example of such a lesion in MPD and explains a mechanism for the occurrence of biallelic JAK2 V617F mutation. We have shown that SNP-A can replace the cumbersome microsatellite analysis used initially to identify UPD9p allowing efficient detection of this and other areas of UPD in MPD and other related conditions.4 In general, identification of UPD loci may facilitate discovery of candidate genes contained in the commonly affected areas of copy-neutral LOH that are at risk for biallelic mutations, including FLT3 (UPD13q) and RUNX1 (UPD21q) among the most instructive examples.5

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References

  1. Szpurka H, Tiu R, Murugesan G, Aboudola S, Hsi ED, Theil KS et al. Refractory anemia with ringed sideroblasts associated with marked thrombocytosis (RARS-T), another myeloproliferative condition characterized by JAK2 V617F mutation. Blood 2006; 108: 2173–2181.

    Article  CAS  Google Scholar 

  2. Pardanani AD, Levine RL, Lasho T, Pikman Y, Mesa RA, Wadleigh M et al. MPL515 mutations in myeloproliferative and other myeloid disorders: a study of 1182 patients. Blood 2006; 108: 3472–3476.

    Article  CAS  Google Scholar 

  3. Pikman Y, Lee BH, Mercher T, McDowell E, Ebert BL, Gozo M et al. MPLW515L is a novel somatic activating mutation in myelofibrosis with myeloid metaplasia. PLoS Med 2006; 3: e270.

    Article  Google Scholar 

  4. Gondek LP, Dunbar AJ, Szpurka H, McDevitt MA, Maciejewski JP . SNP array karyotyping allows for the detection of uniparental disomy and cryptic chromosomal abnormalities in MDS/MPD-U and MPD. PLoS ONE 2007; 2: e1225.

    Article  Google Scholar 

  5. Fitzgibbon J, Smith LL, Raghavan M, Smith ML, Debernardi S, Skoulakis S et al. Association between acquired uniparental disomy and homozygous gene mutation in acute myeloid leukemias. Cancer Res 2005; 65: 9152–9154.

    Article  CAS  Google Scholar 

  6. Yamamoto G, Nannya Y, Kato M, Sanada M, Levine RL, Kawamata N et al. Highly sensitive method for genomewide detection of allelic composition in nonpaired, primary tumor specimens by use of affymetrix single-nucleotide-polymorphism genotyping microarrays. Am J Hum Genet 2007; 81: 114–126.

    Article  CAS  Google Scholar 

  7. Schnittger S, Bacher U, Haferlach C, Dengler R, Krober A, Kern W et al. Detection of an MPLW515 mutation in a case with features of both essential thrombocythemia and refractory anemia with ringed sideroblasts and thrombocytosis. Leukemia 2008; 22: 453–455.

    Article  CAS  Google Scholar 

  8. Schmitt-Graeff AH, Teo SS, Olschewski M, Schaub F, Haxelmans S, Kirn A et al. JAK2V617F mutation status identifies subtypes of refractory anemia with ringed sideroblasts associated with marked thrombocytosis. Haematologica 2008; 93: 34–40.

    Article  CAS  Google Scholar 

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Acknowledgements

This study was supported by NIH R01 HL082983 (JPM), U54 RR019391 (JPM), K24 HL077522 (JPM), Award from AA and MDS International Foundation and a charitable donation from the Robert Duggan Cancer Research Fund.

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Authors and Affiliations

  1. Department of Blood Disorders and Hematologic Malignancies, Experimental Hematology and Hematopoiesis Section, Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH, USA

    H Szpurka, L P Gondek, S R Mohan & J P Maciejewski

  2. Department of Clinical Pathology, Cleveland Clinic, Cleveland, OH, USA

    E D Hsi & K S Theil

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  1. H Szpurka
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  2. L P Gondek
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  4. E D Hsi
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  6. J P Maciejewski
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Correspondence to J P Maciejewski.

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Szpurka, H., Gondek, L., Mohan, S. et al. UPD1p indicates the presence of MPL W515L mutation in RARS-T, a mechanism analogous to UPD9p and JAK2 V617F mutation. Leukemia 23, 610–614 (2009). https://doi.org/10.1038/leu.2008.249

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