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Year : 2015  |  Volume : 6  |  Issue : 2  |  Page : 79-81

Chronic eosinophilic leukemia with Fip 1-like 1-platelet-derived growth factor receptor alpha mutation: A rare case report

Army Hospital Research and Referral, Delhi Cantonment, New Delhi, India

Date of Web Publication7-Jul-2015

Correspondence Address:
Khushboo Dewan
26, Amit Apartments, Sector-13, Rohini, Delhi Cantonment, New Delhi - 110 085
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/1658-5127.160207

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Chronic eosinophilic leukemia (CEL) is a rare cause of eosinophilia. CEL is known to be associated with BCR-ABL fusion gene or rearrangement of platelet-derived growth factor receptor alpha (PDGFRA), (Platelet-derived growth factor receptor betaPDGFRB or fibroblast growth factor receptor-1. CEL, no specific type excludes patients with the above mutations and necessitates the presence of clonal cytogenetic abnormality or blast cells more than 2% in peripheral blood and more than 5% in bone marrow. Imatinib mesylate inhibits Fip 1-like 1 (FIP1L1)-PDGFRA-induced colony formation, enabling cells to undergo normal differentiation. Our patient was diagnosed as a case of CEL on clinical grounds along with bone marrow morphology, and imatinib therapy was initiated empirically. Results of FIP1L1-PDGFRA gene rearrangements available subsequently were in concordance with patient profile and response to imatinib therapy.

Keywords: Chronic eosinophilic leukemia, FIP1L1-PDGFRA, hyper eosinophilic syndrome, imatinib mesylate

How to cite this article:
Dewan K, Chatterjee CT. Chronic eosinophilic leukemia with Fip 1-like 1-platelet-derived growth factor receptor alpha mutation: A rare case report. J Appl Hematol 2015;6:79-81

How to cite this URL:
Dewan K, Chatterjee CT. Chronic eosinophilic leukemia with Fip 1-like 1-platelet-derived growth factor receptor alpha mutation: A rare case report. J Appl Hematol [serial online] 2015 [cited 2022 Sep 27];6:79-81. Available from: https://www.jahjournal.org/text.asp?2015/6/2/79/160207

  Introduction Top

Hypereosinophilic syndrome (HES) and chronic eosinophilic leukemia (CEL) are rare chronic disorders with eosinophil overproduction in the bone marrow, which results in marked and sustained peripheral blood eosinophilia. [1] CEL requires positive identification of features indicative of leukemia, such as increased blast cells or evidence of clonality. [1],[2] CEL associated with Fip 1-like 1 (FIP1L1), and platelet-derived growth-factor receptor alpha (PDGFRA) occurs due to a cytogenetically cryptic interstitial deletion involving chromosome 4q12. [1],[2],[3] Imatinib mesylate inhibits FIP1L1-PDGFRA-induced colony formation enabling cells to undergo normal differentiation. [2] We present a case of 34-year-old male diagnosed as chronic eosinophilic leukemia on peripheral blood and bone marrow examination and started empirically on imatinib mesylate therapy. The FIP1L1-PDGFRA fusion protein was detected by reverse transcriptase-polymerase chain reaction (RT-PCR) later.

  Case report Top

A 34-year-old male patient presented with productive cough, fever, and right lung basal crepitations were noted on auscultation. Peripheral blood examination revealed the eosinophilia with 32% eosinophils and absolute eosinophil count of 2100 cells/μL. Appropriate investigations were done, and reactive causes of eosinophilia were ruled out. He was diagnosed as a case of pulmonary eosinophilia and started on diethylcarbamazine. After 4 weeks of therapy, his absolute eosinophil count was 2445 cells/μL and chest radiograph revealed bilateral diffuse nodular opacities. On high resolution computed tomography, extensive patchy areas of ground glass and centrilobular nodular opacities involving all lobes of both lungs were found along with branching linear opacities and interlobular septal thickening. Spirometry showed a restrictive pattern and moderate impairment of diffusion. Fiber-optic bronchoscopy revealed a normal tracheobronchial tree. Broncho-alveolar fluid cytology revealed numerous eosinophils. Trans-bronchial lung biopsy revealed peribronchial inflammatory infiltrate and fibrosis. Meanwhile, his absolute eosinophil count was constantly rising, indicating unresponsiveness to diethylcarbamazine.

A careful peripheral blood smear examination revealed dyspoietic eosinophils and its precursors constituting 95% of all white blood cells (WBCs). Numerous bilobed, trilobed, and quadrilobate forms along with increased granulations were seen [Figure 1]. Bone marrow examination [Figure 2] revealed a hypercellular bone marrow with a myeloid erythroid ratio of 20:1 and increase in hyperlobated eosinophilic precursors. However, there were no blasts both in peripheral smear as well as in the bone marrow. Ultrasonogram abdomen revealed splenomegaly. Echocardiography revealed a thickened and fixed posterior mitral leaflet with doming of anterior mitral leaflet and mitral regurgitation without any evidence of endomyocardial fibrosis. PCR for JAK-2 V617 F mutation revealed a wild-type gene. No BCR-ABL transcripts were detected by real-time quantitative-PCR. Although monoclonality of the eosinophilic lineage was not yet proven, treatment with imatinib 100 mg was started empirically on clinical and bone marrow results. The eosinophil count came down dramatically to 04% in duration of 3 days. Nested RT-PCR for FIP1L1-PDGFRA gene rearrangement revealed the presence of the amplified product indicating the presence of FIP1L1-PDGFRA fusion gene.
Figure 1: Peripheral blood smear of the patient (×400) showing mature eosinophils with nuclear hypersegmentation and hyposegmentation, cytoplasmic vacuolation, and sparse granulation

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Figure 2: Bone marrow biopsy (×400) is hypercellular with eosinophils and eosinophilic precursors

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  Discussion Top

Eosinophilia is defined as an eosinophil count of >0.6 × 10 9 /μL. In an individual presenting with eosinophilia, the first step is to rule out the reactive causes of eosinophilia. [2]

If eosinophilia is not reactive and there is no evidence of clonality or increase in blasts in peripheral blood or bone marrow along with signs of organ involvement and dysfunction, a diagnosis of idiopathic HES is made. [1] If organ involvement is absent, but the other criteria are met, a diagnosis of idiopathic hypereosinophilia is more appropriate. [1] When clonality of the eosinophils is proved, or an increase in myeloblasts is noted in the peripheral blood or the bone marrow, diagnosis of CEL is given. [1],[2] CEL is known to be associated with BCR-ABL fusion gene or rearrangement of PDGFRA, PDGFRB or fibroblast growth factor receptor-1. CEL, no specific type excludes patients with the above mutations. [1],[2]

Cases with the FIP1L1-PDGFRA fusion have a significantly higher absolute blood eosinophil count and eosinophil percentage. [4] However, there is no significant difference in total WBC count. [5] FIP1L1-PDGFRA positive CEL responds poorly to steroids, hydroxyurea or interferon-a, and have a high probability of eosinophilic endomyocarditis and disease-related death. In FIP1L1-PDGFRA positive CEL, palpable splenomegaly, markedly increased serum Vitamin B12, and marrow biopsies revealing a distinctively myeloproliferative aspect are present. [6]

Peripheral blood smear of a patient with CEL reveals mainly mature eosinophils with small numbers of eosinophilic precursors. Eosinophils reveal sparse granulation, with clear areas of cytoplasm, cytoplasmic vacuolations, nuclear hypersegmentation or hyposegmentation and enlarged size. Neutrophilia, monocytosis, and mild basophilia may be seen. Bone marrow is hypercellular due to eosinophilic proliferation. Charcot Leyden crystals are often present. Myeloblasts (5-19%) may be present. Marrow fibrosis may be seen due to eosinophil basic protein and eosinophil cationic protein. [1],[2]

Imatinib's efficacy in patients with CEL and HES has led to the identification of FIP1L1-PDGFRA as a pathogenetically relevant tyrosine kinase. This case report further reinforces the role of imatinib in patients with F1P1L1-PDGFRA gene rearrangement. The patient responded to imatinib symptomatically as well as in the form of decreased absolute eosinophil count even before the gene rearrangement was detected. The diagnosis of CEL although rare should always be kept in mind when dealing with a case of eosinophilia.

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Conflicts of Interest

There are no conflicts of interest.

  References Top

Swerdlow S, Harris NL, Stein H, Jaffe ES, Theile J, Vardiman JW. World Health Organization Classification of Tumours. Pathology and Genetics of Tumours of Haematopoietic and Lymphoid Tissues. Lyon, France: IARC Press; 2008. p. 51-3.  Back to cited text no. 1
Gotlib J. World Health Organization-defined eosinophilic disorders: 2011 update on diagnosis, risk stratification, and management. Am J Hematol 2011;86:677-88.  Back to cited text no. 2
Tefferi A, Gotlib J, Pardanani A. Hypereosinophilic syndrome and clonal eosinophilia: Point-of-care diagnostic algorithm and treatment update. Mayo Clin Proc 2010;85:158-64.  Back to cited text no. 3
Wang LN, Pan Q, Fu JF, Shi JY, Jin J, Li JM, et al. FIP1L1-PDGFRalpha alone or with other genetic abnormalities reveals disease progression in chronic eosinophilic leukemia but good response to imatinib. Chin Med J (Engl) 2008;121:867-73.  Back to cited text no. 4
Jovanovic JV, Score J, Waghorn K, Cilloni D, Gottardi E, Metzgeroth G, et al. Low-dose imatinib mesylate leads to rapid induction of major molecular responses and achievement of complete molecular remission in FIP1L1-PDGFRA-positive chronic eosinophilic leukemia. Blood 2007;109:4635-40.  Back to cited text no. 5
Vandenberghe P, Wlodarska I, Michaux L, Zachée P, Boogaerts M, Vanstraelen D, et al. Clinical and molecular features of FIP1L1-PDFGRA (+) chronic eosinophilic leukemias. Leukemia 2004;18:734-42.  Back to cited text no. 6


  [Figure 1], [Figure 2]


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