| Abstract|| |
Chronic lymphocytic leukemia (CLL) is the most common leukemia of adults in the western world and constitutes about 33% of all leukemia's. The incidence of CLL increases with age and are more common in older population. Chronic myeloid leukemia (CML) on the contrary occurs in both young adults and elderly and is a chronic myeloproliferative disease that originates from abnormal pluripotent stem cells and results in involvement of multiple hematopoietic lineages, but predominantly myeloid and less commonly lymphoid. Association between CLL and myeloid malignancies (CML, acute myeloid leukemia and MDS, myelodysplastic syndrome) is rare. In literature documenting CLL and CML in same patients, occur either simultaneously or CML is preceded by CLL.
Keywords: CLL, CML, secondary leukemia, cytokines
|How to cite this article:|
Bhattacharyya PK. Occurrence of chronic lymphocytic leukemia in patients with chronic myelogenous leukemia
. Indian J Pathol Microbiol 2013;56:188-9
| Discussion|| |
Patients with chronic myeloid leukemia (CML) have a natural history of evolution to blast crisis and are less commonly associated with a secondary non-myeloid malignancy. Although uncommon, occurrence of secondary cancer other than blast crisis is known to occur in patients with initial diagnosis of CML or other myeloproliferative disorder. Recently published data from MD Anderson Cancer Center (Verma et al.), studied 1445 cases of CML/myeloproliferative neoplasm (MPN) or other hematologic malignancies on tyrosine kinase inhibitor. After 107 months median follow-up of CML/MPN revealed that 66 patients (4.6%), developed secondary cancers. Most of these were solid tumors, such as skin cancer (13%), prostate cancer (15%) and melanoma (13%) and digestive tract cancer (10%). Secondary cancer involving kidney, thyroid and breast occurred in 3-4% cases. Chronic lymphocytic leukemia (CLL) following CML was uncommon. 
Unlike CML, the oncogenic effect of chemotherapy to CLL protocol predisposes to development of many secondary cancers. Both chlorambucil and radiation predisposes to secondary malignancy. The immune deficiency associated with CLL also predispose to secondary cancer. The second malignancy in the majority of cases is non-hematologic and occurs usually several years after the diagnosis of CLL.
In most cases reported in the literature, CLL preceded the development of CML or both leukemias developed simultaneously. ,,, Development of CML and CLL in a patient is believed to be facilitated by interaction between lymphoid and myeloid lineages. Breakpoint cluster region-Abelson murine leukemia viral oncogene homolog 1 (BCR/ABL)-transformed cells in experimental mice model secrete a number cytokine including interleukin 3 (IL3). Cytokine IL3 is believed in experimental model to stimulate production of B lymphoid cells from human CD34 (+), CD38 (-) precursor stem cells. These mechanisms may play a role in developing CLL in a patient with established CML.
Until now, there have been only few well documented, reported instances of CLL developing after the diagnosis of CML. ,, In all of these three cases, the patients were in the chronic phase of CML and CLL developed 20 and 36 months after the onset of CML. In all documented patients, CML and CLL arose from distinct clones with two distinct lineage associated genomic events. , Whether this finding signifies a defective stem cell micro-environment that triggers development of leukemias or whether two distinct events occurred simply by co-incidence in the same individual warrants further study and needs further clarification.
This present case is another  well-documented case of CLL following diagnosis of CML in accelerated phase, with review of literature. The time interval between the diagnosis initial CML on Accelerated Phase and development CLL was only 8 months in this case. Although IgH rearrangement was not performed, clonality of B cell CLL in this case, was documented by flow cytometric analysis with kappa light chain restriction. CML clone was considered absent by demonstration of negative cytogenetic study and BCR/ABL negativity by reverse transcriptase-polymerase chain reaction (cytogenetic and molecular remission of CML) at the time of diagnosis of CLL.
Some published case studies, in which patients with coexistent CLL and CML were studied at the genomic level, already hypothesized that the two diseases originate in two different cell clones, as indirectly suggested by the negativity of a molecular marker in one of the two clones examined. ,,
| References|| |
|1.||Verma D, Kantarjian H, Strom SS, Rios MB, Jabbour E, Quintas-Cardama A, et al. Malignancies occurring during therapy with tyrosine kinase inhibitors (TKIs) for chronic myeloid leukemia (CML) and other hematologic malignancies. Blood 2011;118:4353-8. |
|2.||Esteve J, Cervantes F, Rives S, Rozman M, Zarco MA, Montserrat E. Simultaneous occurrence of B-cell chronic lymphocytic leukemia and chronic myeloid leukemia with further evolution to lymphoid blast crisis. Haematologica 1997;82:596-9. |
|3.||Crescenzi B, Sacchi S, Marasca R, Temperani P, La Starza R, Matteucci C, et al. Distinct genomic events in the myeloid and lymphoid lineages in simultaneous presentation of chronic myeloid leukemia and B-chronic lymphocytic leukemia. Leukemia 2002;16:955-6. |
|4.||Mansat-De Mas V, Rigal-Huguet F, Cassar G, Kuhlein E, Laurent G, Dastugue N. Chronic myeloid leukemia associated with B-cell chronic lymphocytic leukemia: Evidence of two separate clones as shown by combined cell-sorting and fluorescence in situ hybridisation. Leuk Lymphoma 2003;44:867-9. |
|5.||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 Clin Oncol 2012;30:e327-30. |
|6.||Salim R, Wang L, Lin K, Clark RE. Chronic lymphocytic leukaemia developing in the course of chronic myeloid leukaemia. Leuk Lymphoma 2002;43:2225-7. |
|7.||Gargallo P, Cacchione R, Chena C, Dupont J, Garay G, Riveros D, et al. Chronic lymphocytic leukemia developing in a patient with chronic myeloid leukemia: Evidence of distinct lineage-associated genomic events. Cancer Genet Cytogenet 2005;161:74-7. |
|8.||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. |
|9.||Narender K, Jasmina A, Pankaj M, Man Uh Singh Sachdeva. Chronic lymphocytic leukemia developing in a case of chronic myelogenous leukemia - accelerated phase: A rare case with review of the literature. IJPM 2013;56:301-3. |
Pritish K Bhattacharyya
Department of Pathology, Hackensack University Medical Center, Rutgers New Jersey Medical School, 30 Prospect Avenue, Hackensack, NJ 07601
Source of Support: None, Conflict of Interest: None