Scholarlink

<p>Lineage switch in acute leukemia is a rare but clinically significant event characterized by transformation of leukemic blasts from lymphoid to myeloid lineage or vice versa during relapse, reflecting underlying clonal plasticity and therapeutic selection pressure. We report four cases encountered at our institution illustrating diverse biological contexts of lineage switch. Three patients were initially diagnosed with B-cell precursor acute lymphoblastic leukemia (BCP-ALL) and subsequently relapsed as acute myeloid leukemia (AML), while one patient with primary AML relapsed with emergence of a B-lineage blast population consistent with mixed phenotypic evolution. Two cases demonstrated KMT2A rearrangements at relapse, supporting lineage promiscuity associated with primitive progenitors. One patient with BCR::ABL1-positive BCP-ALL and monosomy 7 lost the BCR::ABL1 fusion at relapse and acquired two pathogenic RUNX1 mutations (p.Arg232Trp, VAF 15.33%; p.Gly199Val, VAF 14.26%), indicating true clonal evolution rather than phenotypic drift. In the post-transplant setting, lineage switch was accompanied by declining donor chimerism, assisting in distinguishing relapse from donor-derived leukemia. Immunophenotypic shifts consistently demonstrated loss of lineage-defining markers with acquisition of alternate lineage antigens. Venetoclax-based salvage regimens were administered in relapsed cases; however, outcomes remained poor, with two early post-switch deaths and one patient requiring a second transplant to achieve remission. These cases underscore the aggressive biology, molecular instability, and therapeutic challenges associated with lineage switch and highlight the importance of comprehensive reassessment at relapse integrating morphology, multiparametric flow cytometry, cytogenetics, molecular profiling, and chimerism analysis.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Lineage Switch in Acute Leukaemia: A Four-Case Series Highlighting Clonal Evolution and Post-Transplant Plasticity

  • 期刊论文

  • 发表日期：

    2026年6月20日

查看全文
  • Avik Basu,
  • Asish Rath,
  • Rakesh Bhagwan Demde,
  • Munmun Banerjee,
  • Sambhunath Banerjee,
  • Mayur Parihar

摘要

Lineage switch in acute leukemia is a rare but clinically significant event characterized by transformation of leukemic blasts from lymphoid to myeloid lineage or vice versa during relapse, reflecting underlying clonal plasticity and therapeutic selection pressure. We report four cases encountered at our institution illustrating diverse biological contexts of lineage switch. Three patients were initially diagnosed with B-cell precursor acute lymphoblastic leukemia (BCP-ALL) and subsequently relapsed as acute myeloid leukemia (AML), while one patient with primary AML relapsed with emergence of a B-lineage blast population consistent with mixed phenotypic evolution. Two cases demonstrated KMT2A rearrangements at relapse, supporting lineage promiscuity associated with primitive progenitors. One patient with BCR::ABL1-positive BCP-ALL and monosomy 7 lost the BCR::ABL1 fusion at relapse and acquired two pathogenic RUNX1 mutations (p.Arg232Trp, VAF 15.33%; p.Gly199Val, VAF 14.26%), indicating true clonal evolution rather than phenotypic drift. In the post-transplant setting, lineage switch was accompanied by declining donor chimerism, assisting in distinguishing relapse from donor-derived leukemia. Immunophenotypic shifts consistently demonstrated loss of lineage-defining markers with acquisition of alternate lineage antigens. Venetoclax-based salvage regimens were administered in relapsed cases; however, outcomes remained poor, with two early post-switch deaths and one patient requiring a second transplant to achieve remission. These cases underscore the aggressive biology, molecular instability, and therapeutic challenges associated with lineage switch and highlight the importance of comprehensive reassessment at relapse integrating morphology, multiparametric flow cytometry, cytogenetics, molecular profiling, and chimerism analysis.