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Table of Contents 
CASE REPORT
Year : 2011  |  Volume : 56  |  Issue : 4  |  Page : 423-425
Chronic myeloid leukemia in an adult ghanaian with sporadic neurofibromatosis 1


1 Department of Haematology, University of Ghana Medical School, Accra, Ghana
2 Department of Haematology, Korle Bu Teaching Hospital, Accra, Ghana

Date of Web Publication10-Sep-2011

Correspondence Address:
Edeghonghon E Olayemi
Department of Haematology, University of Ghana Medical School, P.O. Box 4236, Korle Bu, Accra
Ghana
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0019-5154.84747

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   Abstract 

Patients with neurofibromatosis type 1 (NF1), a common, progressive, autosomal dominant neurocutaneous disorder, are predisposed to malignancies. Several types of hematologic malignancies have been described in them. However, to date there has been no report to the best of our knowledge of a patient with NF1 developing chronic myeloid leukemia (CML). We present an adult Ghanaian with NF1, who subsequently developed CML. Relevance of the case report is discussed.


Keywords: Adult Ghanaian, chronic myeloid leukemia, sporadic neurofibromatosis


How to cite this article:
Olayemi EE, Benneh AA, Acquah ME, Mensah PK. Chronic myeloid leukemia in an adult ghanaian with sporadic neurofibromatosis 1. Indian J Dermatol 2011;56:423-5

How to cite this URL:
Olayemi EE, Benneh AA, Acquah ME, Mensah PK. Chronic myeloid leukemia in an adult ghanaian with sporadic neurofibromatosis 1. Indian J Dermatol [serial online] 2011 [cited 2019 Nov 17];56:423-5. Available from: http://www.e-ijd.org/text.asp?2011/56/4/423/84747



   Introduction Top


Neurofibromatosis type 1 (NF1) is a common, progressive, autosomal dominant neurocutaneous disorder characterized by variable expressivity and a predisposition to the development of tumors. It is sporadic in about 50% of cases and affects 1 in 4000 individuals. Clinical features include cafe΄-au-lait macules, skin-fold freckles, Lisch nodules, and dermal neurofibromas. [1]

Chronic myeloid leukemia (CML) is a clonal stem cell disorder characterized by increased proliferation of myeloid cells and the presence of Philadelphia chromosome. It is a common hematological malignancy. The natural history of CML is one of progression from a chronic phase via an accelerated phase to blast crisis, the blast crises is often refractory to treatment. Demonstration of the presence of Philadelphia chromosome is diagnostic. This chromosome leads to reciprocal translocation between chromosomes 9 and 22, juxtaposing the BCR and ABL genes onto chromosome 22, producing a fusion protein with abnormal tyrosine kinase activity; [2] leading to a proliferative advantage in the affected cells. [3]

Children with NFI have about 500 times greater risk of developing a malignant myeloid disorder than the normal children. [4] NF-1 has been associated with nonlymphocytic leukemia such as juvenile myelomonocytic leukemia, myelodysplastic syndrome, and acute myeloid leukemia (AML) in children. [4],[5] Childhood acute lymphoblastic leukemia (ALL) has been reported rarely in association with familial NF-1, with sporadic NF-1 showing a higher incidence of ALL than nonlymphocytic leukemia. [6] The ratio of ALL to nonlymphocytic leukemia patients was 5:3 among sporadic NF-1 and 4:15 among patients with familial NF-1. [5]

However, this association between NF1 and malignant blood disorders has rarely been demonstrated in adults. [4] A study by Julia et al. reported two adults who developed AML over a 10-year period, none developed CML, ALL, or chronic lymphocytic leukemia. [4] Increased levels of Ras-GTP are found in the NF1-associated leukemias, these leukemic cells show hypersensitivity to GM-CSF and other cytokines. [6] A literature search carried out in PubMed did not reveal any report of CML in adults with NF1. We present a patient with sporadic NF1 who subsequently developed CML.


   Case Report Top


Our patient was a 37-year old female teacher who was first seen in the hematology outpatient clinic following a referral from the dermatology clinic where she was being managed for type 1 neurofibromatosis (NF1). She presented with a 6-month history of easy fatigability and a left-sided abdominal mass. She had lost more than 10% of her weight in the past 6 months, and also complained of night sweats. Our patient was married with three children; there was no history of NF in either her nuclear or extended family.

On examination, she was chronically ill-looking and pale, afebrile to touch with Café-au lait spots over her trunk and lower limb, she also had neufibromas over her trunk [Figure 1]. Her spleen was enlarged 16 cm below the left costal margin. There was no hepatomegaly.
Figure 1: Presence of neurofibroma on the patient's back

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The result of her full blood count is shown in [Figure 2], peripheral blood film and marrow aspirate were consistent with CML in chronic phase [Figure 3]. A FISH analysis for BCR/ABL translocation showed that all 200 of her cells screened were positive for the BCR/ABL signal.
Figure 2: Result of full blood count done for the patient over time

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Figure 3: Bone marrow aspirate cytology showing spectrum of myeloid maturation

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While awaiting her FISH analysis result, she was started on 2 g hydroxyurea (HU) daily, 300 mg allopurinol daily, and liberal oral fluids of at least 3L over 24 h. She was on hydroxyurea for about 6 months with fairly good results as shown in [Figure 2]. When her FISH result was obtained, she was subsequently placed on 400 mg glivec daily. The patient did not tolerate glivec for very long, as she developed a pancytopenia, worst affected were the platelet count, she then started bleeding from the gums and developed menorrhagia, clotting profile done was normal apart from the presence of thrombocytopenia. Glivec was stopped and she was recommenced HU with poorer results this time, WBC did not respond and continued to rise.

Bone marrow aspirate confirmed that she had progressed into the blast state attempts at inducing remission with AML regimen failed.


   Discussion Top


The NF1 gene (a tumor suppressor gene) encodes neurofibromin which has a GTPase-activating protein (GAP) domain that regulates the action of Ras proteins. [6] Ras proteins are signal switch molecules regulating cycling between an active guanosine triphosphate (GTP)-bound state (Ras-GTP) and an inactive guanosine diphosphate (GDP)-bound state (Ras-GDP). [7] Ras activation is an essential component of proliferative responses of cells to extracellular stimuli. [7] The absence of neurofibromin predisposes to tumor formation. As a result, people with NF1 are at increased risk for the development of malignancies such as leukemia, rhabdomyosarcoma, optic glioma, and brain tumors. [8]

Given the relative common incidence of NF1 and the fact that patients with this disease have been shown by several authors to be predisposed to developing malignant diseases, it is difficult not to associate the CML which our patient developed with the underlying NF1 process; although to the best of our knowledge this association has not been previously made in an adult. It is possible that there was a synergistic action between the absence of neurofibromin and the presence of the tyrosine kinase activity of the BCR/ABL gene.

We are unable to explain why she ran a rather poor course, since other patients with CML and the Philadelphia chromosome have fared a lot better when placed on Glivec.

We conclude that dermatologist and other physicians that mange patients with NF1 should remain at alert about the possibility of their patients developing CML along with other malignancies.


   Acknowledgment Top


We wish to thank the Glivec International Patient Assistance Programme (GIPAP) for making Glivec available to our patient.

 
   References Top

1.Yohay K. Neurofibromatosis type 1 and associated malignancies. Curr Neurol Neurosci Rep 2009;9:247-53.  Back to cited text no. 1
[PUBMED]    
2.Joske DJ. Chronic myeloid leukaemia: The evolution of gene-targeted therapy. Med J Aust 2008;189:277-82.  Back to cited text no. 2
[PUBMED]  [FULLTEXT]  
3.Au WY, Caguioa PB, Chuah C, Hsu SC, Jootar S, Kim D, et al. Chronic myeloid leukemia in Asia. Int J Hematol 2009;89:14-23.  Back to cited text no. 3
    
4.Julia A, Ayguasanosa J, Blanco A. Familial neurofibromatosis type I and adult acute lymphocytic leukemia. Haematologica 1999;84:472-3.   Back to cited text no. 4
[PUBMED]  [FULLTEXT]  
5. Gahalaut P, Ali MM. Acute lymphocytic leukemia in sporadic neurofibromatosis. Indian J Dermatol Venereol Leprol 2007;73:267-8.  Back to cited text no. 5
[PUBMED]  Medknow Journal  
6.Korf BR. Malignancy in neurofibromatosis type 1. Oncologist 2000;5:477-85.   Back to cited text no. 6
[PUBMED]  [FULLTEXT]  
7. Lauchle JO, Braun BS, Loh ML, Shannon K. Inherited predispositions and hyperactive Ras in myeloid leukemogenesis. Pediatr Blood Cancer 2006;46:579-85.  Back to cited text no. 7
[PUBMED]  [FULLTEXT]  
8.Pui CH. Acute lymphoblastic leukemia. Pediatr Clin North Am 1997;44:831-46.  Back to cited text no. 8
[PUBMED]    


    Figures

  [Figure 1], [Figure 2], [Figure 3]



 

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    Abstract
   Introduction
   Case Report
   Discussion
   Acknowledgment
    References
    Article Figures

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