Journal of Postgraduate Medicine
 Open access journal indexed with Index Medicus & ISI's SCI  
Users online: 2007  
Home | Subscribe | Feedback | Login 
About Latest Articles Back-Issues Articlesmenu-bullet Search Instructions Online Submission Subscribe Etcetera Contact
 ::  Similar in PUBMED
 ::  Search Pubmed for
 ::  Search in Google Scholar for
 ::  Article in PDF (361 KB)
 ::  Citation Manager
 ::  Access Statistics
 ::  Reader Comments
 ::  Email Alert *
 ::  Add to My List *
* Registration required (free) 

  IN THIS Article
 ::  References
 ::  Article Figures

 Article Access Statistics
    PDF Downloaded25    
    Comments [Add]    
    Cited by others 2    

Recommend this journal


  Table of Contents     
Year : 2015  |  Volume : 61  |  Issue : 2  |  Page : 137-138

Development of chronic myelogenous leukemia in a case of chronic lymphocytic leukemia with Tp53 gene deletion

1 Department of Cytogenetics, Tata Medical Center, Kolkata,West Bengal, India
2 Department of Clinical Hematology, Tata Medical Center, Kolkata,West Bengal, India

Date of Web Publication13-Mar-2015

Correspondence Address:
M Parihar
Department of Cytogenetics, Tata Medical Center, Kolkata,West Bengal
Login to access the Email id

Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0022-3859.150907

Rights and Permissions

How to cite this article:
Gupta A, Parihar M, Yadav A K, Chakrapani A. Development of chronic myelogenous leukemia in a case of chronic lymphocytic leukemia with Tp53 gene deletion. J Postgrad Med 2015;61:137-8

How to cite this URL:
Gupta A, Parihar M, Yadav A K, Chakrapani A. Development of chronic myelogenous leukemia in a case of chronic lymphocytic leukemia with Tp53 gene deletion. J Postgrad Med [serial online] 2015 [cited 2023 Jun 2];61:137-8. Available from:

Concurrent manifestation of a myeloid and lymphoid neoplasm is a rare occurrence and is reported in less than 1% of the cases. [1]

A 57 year old patient presented with weakness, lymphadenopathy and hepatosplenomegaly, with a WBC count of 1,51,500/΅L and 92% lymphocytes. Immunophenotyping confirmed the diagnosis of CLL with the neoplastic cells expressing CD19,CD5, CD23, CD79b and CD20. Fluorescence in situ hybridization (FISH) analysis on lymphocytes enriched by lipopolysaccharide-stimulated culture (LSC) showed TP53 deletion in 42% of the interphase cells. On treatment with single agent cyclophosphamide, 24 months post-diagnosis he presented with features of an evolving myeloproliferative neoplasm with a total count of 52,600/μL and a differential count that showed11% immature myeloid precursors,4% basophils and 40% lymphocytes. FISH done on peripheral blood using BCR-ABL1 dual-color dual fusion probe showed BCR-ABL1 fusion positivity in 34% of cells with an atypical single fusion signal pattern (1F2G1R). FISH analysis on lymphocytes enriched by LSC showed TP53 deletion in 15% of the cells. Conventional cytogenetic analysis of metaphases from un-stimulated overnight bone marrow cultures showed a t (9;15)(q34;q22) in 38 of the 40 metaphases with no morphological evidence of a Ph chromosome or deletion of the short arm of chromosome 17 (17p) [Figure 1]a and b].
Figure 1: (a) GTG banded processed metaphase spread from LPS stimulated bone marrow cultures. (b) GTG banded karyogram spread from LPS-stimulated bone marrow cultures showing t(9;15), marked with small arrows, and both normal chromosome 22. Chromosome 17 appears normal. (c) Inverted DAPI FISH image of the same matched metaphase as in Figure 1a using BCR-ABL1 probe from Vysis, Abbott, showing BCR-ABL1 fusion signal located on chromosome 9 instead of chromosome 22. Red signal (ABL1) on normal chromosome 9, fusion signal on involved chromosome 9 and two green signals (BCR) on normal chromosome 22. (d) FISH done on LPS stimulated bone marrow cultures using TP53 probe from Vysis, Abbott, and showing 2 green 1red signal pattern indicating deletion of the TP53 gene in the interphases only

Click here to view

The matched metaphase FISH confirmed the presence of BCR-ABL1fusion, located on derivative chromosome 9 instead of chromosome 22 with green signals on both normal chromosome 22 and one red signal on the normal chromosome 9 (1F2G1R) [Figure 1]c]. Quantitative polymerase chain reaction done on the bone marrow aspirate sample showed the presence of p210 (e13a2) fusion transcript confirming the diagnosis of CML. The patient was started on chlorambucil (author give dose) and 400mg of Imatinib per day. Fifteen months post imatinib, the patient remains in complete cytogenetic remission of the CML clone (FISH negative), with persistent CLL clone,the TP53gene deletion being present in 23% of the cells [Figure 1]d].

Only ten cases of sequential occurrence of CML following CLL have been described in literature. The postulated causes for this are oncogenic effect of chemotherapeutic agents, (cyclophosphamide in the present case), immunodeficiency associated with CLL, defective stem cell pool, age-related accumulation of genetic defects or a common leukemogenic event. [2],[3] Secondary CML developing after CLL usually shows a favorable response to Imatinib. [4]

Our case, besides adding on to the series of CML developing in a diagnosed case of CLL and aberrant location of the BCR-ABL1 fusion gene on chromosome 9 instead of chromosome 22, also provides evidence for separate clonal origin of these neoplasms. Imatinib maintains its therapeutic effectiveness in controlling the CML clone in such an unusual setting though with no effect on CLL clone. The case also emphasizes and reiterates the fact that FISH and karyotyping are complementary to each other and so should be judiciously used together to arrive at a correct diagnosis.

 :: References Top

Laurenti L, Tarnani M, Nichele I, Ciolli S, Cortelezzi A, Forconi F, et al. The coexistence of chronic lymphocytic leukemia and myeloproliperative neoplasms: A retrospective multicentric GIMEMA experience. Am J Hematol 2011;86:1007-12.  Back to cited text no. 1
D'Arena G, Gemei M, Luciano L, D'Auria F, Deaglio S, Statuto T, et al. Chronic lymphocytic leukemia after chronic myeloid leukemia in the same patient: Two different genomic events and a common treatment? J ClinOncol 2012;30:e327-30.   Back to cited text no. 2
Royle JA, Baade PD, Joske D, Girschik J, Fritschi L. Second cancer incidence and cancer mortality among chronic lymphocytic leukaemia patients: A population-based study. Br J Cancer 2011;105:1076-81.   Back to cited text no. 3
Bhagavathi S, Borromeo V, Desai H, Crisan D. Case report and literature review: A rare patient with chronic myeloid leukemia and chronic lymphocytic leukemia. Ann Clin Lab Sci 2008;38:405-9.  Back to cited text no. 4


  [Figure 1]

This article has been cited by
1 A Tale of Two Hematological Malignancies: CML Followed by CLL in the Same Patient
Insija Selene, Aasems Jacob, Zain Mary El-Amir, Sanjivani Sathe, Asma Taj
Annals of Internal Medicine: Clinical Cases. 2023; 2(1)
[Pubmed] | [DOI]
2 Meta-Analysis of Gastrointestinal Adverse Events from Tyrosine Kinase Inhibitors for Chronic Myeloid Leukemia
Prahathishree Mohanavelu, Mira Mutnick, Nidhi Mehra, Brandon White, Sparsh Kudrimoti, Kaci Hernandez Kluesner, Xinyu Chen, Tim Nguyen, Elaina Horlander, Helena Thenot, Vamsi Kota, Cassie S. Mitchell
Cancers. 2021; 13(7): 1643
[Pubmed] | [DOI]


Print this article  Email this article
Online since 12th February '04
2004 - Journal of Postgraduate Medicine
Official Publication of the Staff Society of the Seth GS Medical College and KEM Hospital, Mumbai, India
Published by Wolters Kluwer - Medknow