Diwakar Sharma

Philadelphia (Ph) positive chromosome comprises 90-95% of chronic myeloid leukemia (CML). The remaining 5-10% consists of intricate translocations that may involve a third chromosome. The impact of Tyrosine kinase inhibitor (TKI) treatment on the variant Ph Chromosomes is not known. In this study, we compiled all the reported cases of variants Ph Chromosomes (3 & 4-way translocations) and assessed their primary response as complete remission after TKI treatment. A fifty-five years old female with bone marrow (BM) with a history of Type-II Diabetes mellitus, hypertension, and severe acute corticosteroid Gastritis, was diagnosed as CML-CP with 46, XX, t(9;15;22) (q34;p11;q11) [20] bone marrow cytogenetics. Reverse Transcriptase polymerase chain reaction (qPCR) was positive for e13a2 transcript for translocation BCR-ABL (p210) consisting of 39608.38 absolute ABL1 and 13693.7 absolute BCR-ABL1 copies [(BCR-ABL1/ ABL1) * 100 = 34.57%]. Furthermore, 92% of cells tested positive for BCR-ABL1 translocation by the fluorescent In situ hybridization (FISH) method. The BM flow cytometric immunophenotyping analysis of CML-CP shows approximately 1.8% CD45 dim positive blasts which are CD7+, cCD3+, CD5+, and negative for CD4, CD8, CD2, CD56, and CD34. The spleen enlargement by 14cm in size and no mutation was detected in the BCR-ABL1 kinase domain. The patient’s hematological analysis revealed WBC of 3730 cells/µl, decreased hemoglobin levels of 8.8 g/dl, ANC: P57.3L28.2M7.6, Blood Urea/ Creatinine: 24/ 0.62, Calcium/ Phosphate: 8.8/ 4.0, Uric acid (mg%): 3.2, Na+/ K+: 137/ 4.8, Bilirubin (mg%): 0.6, A/G Ratio: 4, SGOT/ SGPT: 37/ 67, Alk Phos. (Units): 235(<116), S. lipase: 177(<300), and HbAc: 8.7%. Post imatinib mesylate induction, BM was in hematological remission, qPCR ratio (BCR-ABL1/ ABL1) * 100 was 8.55% [transcript major (p210) and minor (p190)] with a CML-CP Sokal index of 0.9. Hematopoietic cells of all series (M : E :: 4 : 1) were seen in the cellular BM preparation, along with 1-2% blasts. In the literature, only 18 cases were reported with 3 (15/18) and 4 (3/18) way BCR-ABL1 translocation. Amongst the 15 cases of 3-way BCR-ABL1 translocation, TKI response data were reported in 11 patients. All patients with 3- and 4-way BCR-ABL1 translocation showed complete response with TKI treatment. The current study describes a rare case with 46:XX; t(9;15;22) (q34;p11;q11) along with CML-CP also showed a complete hematological response to imatinib mesylate.

Audience Takeaway:

• Even after having different complex translocations, CML patients respond to the same and effective Tyrosine Kinase Inhibitor (TKI) treatment. As a result, the patients have a complete haematological response.
• This research will simplify the clinician's job and eliminate the quandary of whether to change the treatment or not, and they will be much more certain about it. Furthermore, it will improve treatment accuracy.
• This study also alerts and encourages researchers to confirm each result using more than one method (As we have done to confirm translocation we have used cytogenetics, FISH, and qPCR).