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LETTER TO THE EDITOR
Year : 2015  |  Volume : 52  |  Issue : 3  |  Page : 323-324
 

p-190 chronic myelogenous leukemia presenting as extramedullary blast crisis


1 Department of Pathology, All India Institute of Medical Sciences, New Delhi, India
2 Department of Medicine, All India Institute of Medical Sciences, New Delhi, India
3 Department of Haematology, All India Institute of Medical Sciences, New Delhi, India

Date of Web Publication18-Feb-2016

Correspondence Address:
R Saxena
Department of Pathology, All India Institute of Medical Sciences, New Delhi
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0019-509X.176712

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How to cite this article:
Langer S, Sharma S, Kapoor R, Subbarao K, Sazawal S, Saxena R. p-190 chronic myelogenous leukemia presenting as extramedullary blast crisis. Indian J Cancer 2015;52:323-4

How to cite this URL:
Langer S, Sharma S, Kapoor R, Subbarao K, Sazawal S, Saxena R. p-190 chronic myelogenous leukemia presenting as extramedullary blast crisis. Indian J Cancer [serial online] 2015 [cited 2019 Sep 18];52:323-4. Available from: http://www.indianjcancer.com/text.asp?2015/52/3/323/176712


Sir,

We present a rare case of Philadelphia negative; p-190 BCR-ABL fusion transcript positive chronic myelogenous leukemia (CML) presenting as extramedullary blast crisis in lymph node.

A 39 years old man presented with weakness body aches and sudden fall in hemoglobin to 5.3 g/dl. In the past he was found to have high leukocyte count at this time his hemoglobin was 11.8 g/dl, total leukocyte count was 1,80,000/μl and platelet count of 360,000/μl, with monocytosis on peripheral smear. At this time patient did not have any organomegaly. His leukocyte alkaline phosphatase (LAP) score was low but cytogenetic studies did not reveal any translocation. Based on these findings he was earlier labeled as a case of Chronic Myelomonocytic Leukemia (CMML) and was treated with hydroxyurea 500 mg BD. A detailed clinical examination was carried out with repeat investigations and diagnosis was reviewed. On examination patient had pallor, generalized lymphadenopathy and splenomegaly. The complete blood counts revealed hemoglobin as 6 g/dl, total leukocyte count 58000/μl and platelet count to be 120,000/μl. Peripheral blood revealed leukocytosis with left shift and absolute monocytosis (absolute monocyte count = 16000/μl. The differential leukocyte count was Neutrophils 49%, Lymphocytes 5%, Eosinophils 8%, Monocytes 20%, Metamyelocytes 15%, and Myelocytes 7%. There was an occasional blast, basophil and nRBC. The red blood cells were normocytic normochromic to macrocytic normochromic Platelets were mildly reduced. The leukocyte alkaline phosphatase(LAP) score was low {13/142 (test/control)}.

Bone marrow examination showed marked myeloproliferation with M:E ratio13:1, the blasts constituted 15% of all nucleated cells [Figure 1] and monocytosis. The cytogenetic studies done on bone marrow sample was reported as normal karyotype (46;XY). Multiplex RT-PCR was carried out on peripheral blood sample for BCR-ABL mutations which in cDNA detected 481 bp fragment that is positive for p190 transcript [Figure 2]. Lymph node biopsy had shown lymph node architect being effaced by blasts [Figure 3]. These were confirmed to be myeloblasts as there was cytoplasmic granular positivity for myeloperoxidase [Figure 3], inset]. The peripheral blood and bone marrow picture together with the molecular studies and lymphnode morphology the diagnosis was reviewed to that of Philadelphia (Ph) negative p-190 BCR-ABL fusion transcript positive CML presenting as extramedullary blast crisis in Lymph Node. Before specific therapy could be started the patient had developed infection and went into sepsis. The patient was managed with supportive treatment for two weeks in the hospital at the end of which he expired.
Figure 1: Bone marrow aspirate with 15% blasts and monocytosis

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Figure 2: Agarose gel analysis for the detection of bcr-abl mutations in cDNA by Multiplex RT-PCR. Lane M, 100-bp ladder; lanes 1–6, samples from CML patients, lane1-positive control for bcr-abl p210 mutation showing 310 bp fragment; Lane 2 - CML sample showing 310 bp fragment (positive for bcr-abl p210 mutation); Lane 3 - CML sample showing 481 bp fragment (positive for p190 mutation) and Lane 5,6 - negative sample; lane B is the negative control; Internal control (800 bp fragment) is seen in all the cases. Arrows indicate the product of amplification

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Figure 3: Nuclear convolutions admixed with few mature appearing lymphocytes; myeloperoxidase showing cytoplasmic granular positivity in the neoplastic cell (inset)

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It is known that in 5-10% of patients of CML, the Philadelphia chromosome is not identified, despite the presence of the associated BCR-ABL molecular abnormality these are then classified as Ph-negative, BCR-ABL-positive CML. This is due to variant translocations which are either simple due to the fusion generated by a small insertion of BCR into ABL or complex translocations involving three chromosomes i.e., 9 and 22 with 3q21,5q31,7q32,8q24,10q22, These cases with variant Ph chromosome, the BCR-ABL rearrangement can be detected by molecular methods or by fluorescence in situ hybridization (FISH).[1] BCR-ABL fusion transcript encoding for p190BCR-ABL (ie, without concurrent expression of the e13a2/e14a2 transcript encoding for p210BCR-ABL) is quite rare.[2],[3],[4]

Many such patients have associated monocytosis with cytomorphologic characteristics that are intermediate between CML and CMML.[5] They tend to be older with median age more than 65 years. These patients show resistance to imatinib, and may not fare much better with secondary tyrosine kinase inhibitor therapy. Resistance to treatment is currently poorly understood and may be mediated by mechanism(s) independent of ABL KD mutations.[3],[4] Therefore these patients need to be identified as high-risk patients, monitored closely for efficacy during therapy with tyrosine kinase inhibitors, and offered stem cell transplant early if eligible for this procedure.

 
  References Top

1.
Valencia A, Cervera J, Such E, Barragán E, Bolufer P, Fuster O, et al. Complex Variant t (9;22) Chromosome Translocations in Five Cases of Chronic Myeloid Leukemia. Adv Hematol 2009;187125.  Back to cited text no. 1
    
2.
Quinta×s-Cardama A, Cortes A. Molecular biology of BC R-ABL1-positive chronic myeloid leukemia. Blood 2009;113:1619-30.  Back to cited text no. 2
    
3.
Verma D, Kantarjian HM, Jones D, Luthra R, Borthakur G, Verstovsek S, et al. Chronic myeloid leukemia (CML) with P190BCR-ABL – analysis of characteristics, outcomes and prognostic significance. Blood 2009;114:2232-5.  Back to cited text no. 3
    
4.
Pardanani A, Tefferi A, Litzow MR, Zent C, Hogan WJ, McClure RF, et al. Chronic myeloid leukemia with p190 BCR-ABL: prevalence, morphology, tyrosine kinase inhibitor response, and kinase domain mutation analysis. Blood 2009;114:3502-3.  Back to cited text no. 4
[PUBMED]    
5.
MeloJ V, Myint H, Galton DA, Goldman JM P190BCR-ABL chronic myeloid leukaemia: The missing link with chronic myelomonocyticleukaemia? Leukemia1994;8:208-11.  Back to cited text no. 5
    


    Figures

  [Figure 1], [Figure 2], [Figure 3]



 

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