Co-existing t(9;14)(q33;q32)/IGH Rearrangement is a Risk Factor for Lymphoid Blast Phase Transformation of Chronic Myeloid Leukemia
Cancer Genetics and Therapeutics
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Primary Categories:
- Cancer
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Secondary Categories:
- Cancer
Introduction:
Secondary genetic abnormalities in addition to increased BCR::ABL1 transcript levels are risk factors for chronic myeloid leukemia (CML) transformation from chronic phase (CP) to blast phase (BP), especially myeloid BP. Risk factors for lymphoid BP are poorly characterized, but some studies have implicated oligoclonal recombination of immunoglobulin genes (IGH, IGK, and IGL). We sought to determine the incidence of IGH rearrangement in CML lymphoid BP cases.
Methods:
We searched our database from January 2011 to September 2024 for BCR::ABL1 FISH positive cases with concurrent 14q abnormalities/IGHr+ confirmed by fluorescence in situ hybridization (FISH). BCR::ABL1 and IGH FISH were performed using a tri-color FISH probe set and breakapart (BAP) FISH probes respectively. Clinicopathologic features and cytogenetic profiles were reviewed and analyzed.
Results:
We identified four (4) patients with concurrent t(9;14)(q33;q32)/IGHr+ and t(9;22)(q34;q11.2)/BCR::ABL1. Patients (2 male and 2 female) had a median age of 63.5 years (range14-64 years). Two patients (1 adult, 1 child) were initially diagnosed with Philadelphia chromosome positive (Ph+) B lymphoblastic leukemia (B-ALL). However, peripheral blood neutrophils harboring BCR::ABL1 were detected after tyrosine kinase inhibitor (TKI) treatment, confirming that the “B-ALL” represented lymphoid BP of CML. Interestingly, two cases had t(9;14)(q33;q32)/IGHr+ and t(9;22)(q34;q11.2)/BCR::ABL1 affecting the same chromosome 9, while both chromosome 9 homologs were involved in IGHr+ or BCR::ABL1 in the other two cases. Acquisition of t(9;14)(q33;q32)/IGHr+ after preexisting t(9;22)(q34;q11.2)/BCR::ABL1, presenting as an associated subclone, was observed in one adult patient, while coexisting t(9;14)(q33;q32)/IGHr+ and t(9;22)(q34;q11.2)/BCR::ABL1 were detected during initial work-up in the remaining 3 cases. The BCR::ABL1 transcripts p210 (n=1), p190 (n=1) and coexisting p190/p210 (n=1) were detected in this cohort. With a median follow up of 83.5 months (range, 1-147 months), 3 patients had achieved complete remission and one patient had relapsed lymphoid BP and was subsequently lost to follow-up.
Conclusion:
Primary or secondary detection of concurrent t(9;14)(q33;q32)/IGHr and t(9;22)(q34;q11.2)/BCR::ABL1 appears to represent a risk factor for lymphoid BP in CML. Some patients present with lymphoid BP, masking an underlying CML.
Secondary genetic abnormalities in addition to increased BCR::ABL1 transcript levels are risk factors for chronic myeloid leukemia (CML) transformation from chronic phase (CP) to blast phase (BP), especially myeloid BP. Risk factors for lymphoid BP are poorly characterized, but some studies have implicated oligoclonal recombination of immunoglobulin genes (IGH, IGK, and IGL). We sought to determine the incidence of IGH rearrangement in CML lymphoid BP cases.
Methods:
We searched our database from January 2011 to September 2024 for BCR::ABL1 FISH positive cases with concurrent 14q abnormalities/IGHr+ confirmed by fluorescence in situ hybridization (FISH). BCR::ABL1 and IGH FISH were performed using a tri-color FISH probe set and breakapart (BAP) FISH probes respectively. Clinicopathologic features and cytogenetic profiles were reviewed and analyzed.
Results:
We identified four (4) patients with concurrent t(9;14)(q33;q32)/IGHr+ and t(9;22)(q34;q11.2)/BCR::ABL1. Patients (2 male and 2 female) had a median age of 63.5 years (range14-64 years). Two patients (1 adult, 1 child) were initially diagnosed with Philadelphia chromosome positive (Ph+) B lymphoblastic leukemia (B-ALL). However, peripheral blood neutrophils harboring BCR::ABL1 were detected after tyrosine kinase inhibitor (TKI) treatment, confirming that the “B-ALL” represented lymphoid BP of CML. Interestingly, two cases had t(9;14)(q33;q32)/IGHr+ and t(9;22)(q34;q11.2)/BCR::ABL1 affecting the same chromosome 9, while both chromosome 9 homologs were involved in IGHr+ or BCR::ABL1 in the other two cases. Acquisition of t(9;14)(q33;q32)/IGHr+ after preexisting t(9;22)(q34;q11.2)/BCR::ABL1, presenting as an associated subclone, was observed in one adult patient, while coexisting t(9;14)(q33;q32)/IGHr+ and t(9;22)(q34;q11.2)/BCR::ABL1 were detected during initial work-up in the remaining 3 cases. The BCR::ABL1 transcripts p210 (n=1), p190 (n=1) and coexisting p190/p210 (n=1) were detected in this cohort. With a median follow up of 83.5 months (range, 1-147 months), 3 patients had achieved complete remission and one patient had relapsed lymphoid BP and was subsequently lost to follow-up.
Conclusion:
Primary or secondary detection of concurrent t(9;14)(q33;q32)/IGHr and t(9;22)(q34;q11.2)/BCR::ABL1 appears to represent a risk factor for lymphoid BP in CML. Some patients present with lymphoid BP, masking an underlying CML.