Ann Lab Med.  2018 Jul;38(4):296-305. 10.3343/alm.2018.38.4.296.

GATA1 Expression in BCR/ABL1-negative Myeloproliferative Neoplasms

• Yang N
• Park S
• Cho MS
• Lee M
• Hong KS
• Mun YC
• Seong CM
• Huh HJ
• Huh J

• KMID: 2408068
• DOI: http://doi.org/10.3343/alm.2018.38.4.296

Abstract

BACKGROUND
This study aimed to determine GATA1 expression levels to better characterize subgroups in BCR/ABL1-negative myeloproliferative neoplasms (MPNs).
METHODS
This study enrolled 49 patients diagnosed as having BCR/ABL1-negative MPN on the basis of the 2016 World Health Organization classification : nine polycythemia vera (PV), 17 essential thrombocythemia (ET), 12 prefibrotic primary myelofibrosis (prePMF), and 11 overt primary myelofibrosis (PMF). Relevant clinical and laboratory data were retrieved from the medical records. The molecular analysis of CALR and MPL mutations and quantification of JAK2 V617F allele burden were performed. GATA1 expression was assessed by an immunohistochemical assay on bone marrow biopsy. GATA1 expression was analyzed serially in 18 patients.
RESULTS
GATA1 expression decreased significantly in PMF compared with that in other subtypes, while no statistical difference was identified between ET and prePMF. GATA1 expression did not differ according to the mutation profiles or the allele burden of JAK2 V617F, but it decreased significantly in patients with overt fibrosis or leukemic transformation.
CONCLUSIONS
Our results suggest that GATA1 expression is significantly low in PMF and decreases with progressive fibrosis and possibly with leukemic transformation, although our attempt to accurately distinguish between subgroups using GATA1 immunohistochemical approach did not achieve statistical significance. A large patient cohort with long term follow-up is required to evaluate the prognostic value of GATA1 expression.

Keyword

Polycythemia vera; Essential thrombocythemia; Prefibrotic primary myelofibrosis; Primary myelofibrosis; GATA1

MeSH Terms

Alleles
Biopsy
Bone Marrow
Classification
Cohort Studies
Fibrosis
Follow-Up Studies
Humans
Medical Records
Polycythemia Vera
Primary Myelofibrosis
Thrombocythemia, Essential
World Health Organization

Figure

• 

  Fig. 1 Representative images of GATA1 immunoexpression in bone marrow biopsy samples according to the intensity of the reaction (×400): (A) negative, (B) weak, (C) moderate, and (D) strong. Megakaryocytes (arrows) are identified by CD61-stained (pink-colored) cytoplasm. GATA1-stained nuclei of megakaryocytes colored light to dark brown depending on the immunointensity. GATA1-stained nuclei are also seen in erythroid cells (arrowhead) without the CD61-positive cytoplasm.

• 

  Fig. 2 Distribution of GATA1 expression according to disease groups (P=0.004).Abbreviations: BHD, benign hematologic disease; CML, chronic myeloid leukemia; ET, essential thrombocythemia; LWOB, lymphoma without bone marrow involvement; PMF, primary myelofibrosis; prePMF, prefibrotic primary myelofibrosis; PV, polycythemia vera.

• 

  Fig. 3 Serial analysis of GATA1 expression, the allele burden of JAK2 V617F, and clinical events in patients with polycythemia vera or essential thrombocythemia.*CALR type 1 mutated; †CALR type 2 mutated; ‡Triple negative.Abbreviations: ET, essential thrombocythemia; F/U, follow-up; mo, month; MF, myelofibrosis; NT, not tested; PV, polycythemia vera.

• 

  Fig. 4 Serial analysis of GATA1 expression, the allele burden of JAK2 V617F, and clinical events in patients with prefibrotic primary myelofibrosis or primary myelofibrosis.*CALR type 1 mutated; †CALR type 2 mutated; ‡Triple negative; §Mutations not tested; ∥JAK2 V617F mutated. Allele burden quantification was not performed.Abbreviations: AML, transformation to acute myeloid leukemia; F/U, follow-up; mo, month; MF, myelofibrosis; NT, not tested; PMF, primary myelofibrosis; prePMF, prefibrotic primary myelofibrosis.

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