Single center experience in treating patients with t(4;14) multiple myeloma with and without planned frontline autologous stem cell transplantation
Multiple myeloma (MM) is a malignant plasma cell condition with variable long-term outcomes. Depending on the patients ’ risk factors, long-term overall survival can range from under 2 years to more than 10 years [1, 2]. One of the most important prognostic factors in this condition is disease cytogenetics, which are now commonly assessed using fluorescent in-situ hybridization (FISH) [1-3]. Amongst all of the cyt ogenetic abnormalities detected by FISH that are deemed as high-risk, translocation of the fibroblast growth factor receptor 3 (FGFR3) and multiple myeloma SET domain (MMSET) on chromosome 4 with the IgH gene on chromosome 14 is the most common, accounting for approximately 12-15% of all new cases o f MM .
Mantle cell lymphoma (MCL) accounts for approximately 6% of all Non-Hodgkin lymphoma (NHL) with a median age at presentation of around 70 years. It is characterised by the t(11;14)(q13:32) translocation which leads to overexpression of cyclin D1 resulting in subsequent dysregulation of the cell cycle and of several intracellular survival pathways. Although the survival of MCL patients has been demonstrated to have improved over the last decade it remains incurable, typically relapsing multiple times with increasingly chemotherapy refractory disease.
The treatment of chronic myelogenous leukemia (CML) with tyrosine kinase inhibitors has been the poster child in the drive to “personalize” cancer therapies by identifying vulnerable molecular targets in different cancers. The results in CML have been somewhat uniquely striking, likely in part because the bcr/abl mutation resulting from the 9;22 translocation is both necessary and sufficient to produce this myeloprolif erative disease in animal models whereas most other cancers have a well characterized “multi-hit” pathogenesis.
The Ten Eleven Translocation (TET) enzymes have been found to be mutated in both diffuse large B-cell (DLBCL) and peripheral T-cell (PTCL) lymphomas resulting in DNA hypermethylation. Various important tumor suppressor genes, such as SMAD1 (part of TGF- β signaling), are under-expressed due to aberrantly methylated promoters or enhancers. Recent studies in embryonal stem cells showed that ascorbic acid (AA) is a cofactor for TET with a binding site at the catalytic domain, and enhances TET activity.
Publication date: August 2017 Source:Clinical Lymphoma Myeloma and Leukemia, Volume 17, Issue 8 Author(s): Ching-Hon Pui, Kathryn G. Roberts, Jun J. Yang, Charles G. Mullighan Philadelphia chromosome–like acute lymphoblastic leukemia (Ph-like ALL) is a recently described B-cell precursor ALL with a gene expression profile and a high frequency of IKZF1 gene alteration similar to that of Ph-positive ALL. Its prevalence is approximately 12% in children, 21% in adolescents (16-20 years of age), and 20% to 24% in adults older than 40 years, with a peak (27%) in young adults 21 to 39 years old. It occurs more often in mal...
Publication date: Available online 21 June 2017 Source:Clinical Lymphoma Myeloma and Leukemia Author(s): Chadi Nabhan, Anthony R. Mato Double Hit Lymphomas (DHL) are a new category in the World Health Organization newest classification for lymphoid malignancies. DHL encompasses various histologies of lymphomas where the MYC oncogene and either BCL2 or BCL6 oncogenes are present concomitantly. Several observational studies and retrospective series have demonstrated that DHL patients carry poor prognosis, respond less, and for a shorter duration to standard R-CHOP (rituximab, cyclophosphamide, vincristine, Adriamycin, and p...
• This is an unique case of CML in chronic phase with both the Philadelphia chromosome as well as t(11;14) at initial diagnosis.• Translocation t(11;14)(q13;q32) CCND1-IGH is typically associated with mantle cell lymphoma or a subset of plasma cell myeloma and is exceedingly rare in myeloid neop lasm.• Most likely, the Philadelphia chromosome is the primary cytogenetic abnormality also called the “driver” mutation and the t(11;14)(q13;q32) the secondary or “passenger” mutation in this case. Upregulated cyclin D1 may further promote cells go into cell cycle, thus it may render high er ...
Conclusion This is a largest series of variant translocations in CML-CP, pertaining to Indian population. Our data suggests that presence of variant Ph translocations in CML has no significant impact in predicting response to imatinib as well as in prognosticating survival. Teaser Chronic myeloid leukemia with variant translocation in imatinib era has been an area of research regarding its predictive and prognostic effect with current treatment. Our data confirms that use of imatinib overcomes the negative prognostic effect of these translocations giving similar response rates and survival outcomes.
Chronic myeloid leukemia with variant translocation in imatinib era has been an area of research regarding its predictive and prognostic effect with current treatment. Our data confirms that use of imatinib overcomes the negative prognostic effect of these translocations giving similar response rates and survival outcomes.
Translocation (4;14) is identified by FISH cytogenetics in approximately 15% of myeloma patients (pts). Pts have a poor outcome with initial response to induction chemotherapy but followed by rapid relapse and resistance to alkylating agents. We reviewed outcomes of 74 consecutive myeloma pts with t(4;14) between October 2002 and July 2012. Our goal was to evaluate the impact of pts characteristics on OS and to assess outcome according to treatments received. Clinical characteristics are presented in Table 1.
Analysis of cytogenetic abnormalities in multiple myeloma (MM) currently represents one of the key aspects for prognostic and therapeutic stratification of patients in routine clinical practice. Differentiation of hyperdiploid and nonhyperdiploid state with the most common translocation analysis in IgH gene disruption and assessing other amendments (1q21, del17p) allows individual selection of appropriate therapy. Translocation t(8;14) with rearrangement of MYC oncogene is among the less common cytogenetic changes in MM.