Prolymphocytic Leukemia

TP53-disrupted B-PLL cells showed additional genomic alterations that affect genes implicated in extrinsic and intrinsic apoptotic pathways i.e., TNFRSF10, FAS, MDM2, BCL2, and BCL2L11 and genes involved in cell-cycle regulation i.e., IKBKB, CDK2, CDK4, and RB1, suggesting that a convergent multifactorial pathogenetic mechanism may be involved in B-PLL. Applying the OGM technology on cytogenetically complex rare hematological neoplasia may be useful to improve the genetic definition and differential diagnosis of B PLL/SBLPN and related splenic B cell neoplasms.

Despite a transient response, the disease progressed rapidly. This case underscores the importance of a broad differential diagnosis, judicious use of advanced diagnostics and individualised treatment planning, particularly in rare and aggressive lymphoproliferative disorders.

This brief report describes a patient with T-PLL in whom three distinct abnormal T-cell subsets were delineated by flow cytometric analysis using TRBC1. This case illustrates striking intratumoral heterogeneity in a neoplasm that is typically regarded as phenotypically uniform and demonstrates the utility of TRBC1 analysis in refining diagnostic assessment.

P=N/A, N=200, Recruiting, Masonic Cancer Center, University of Minnesota | Trial completion date: Feb 2027 --> Feb 2028 | Trial primary completion date: Feb 2026 --> Feb 2027

The identification of IGH::TCL1 fusion in these two cases of splenic B-cell lymphoma/leukemia suggests that TCL1 gene rearrangements can occur in B-cell lymphoma/leukemia and should not be considered exclusive to T-cell prolymphocytic leukemia. Accurate diagnosis of splenic B-cell lymphoma/leukemia with TCL1 rearrangement requires evaluation of morphologic and immunophenotypic features and genetic assessment of TCL1.

P2, N=60, Recruiting, Fred Hutchinson Cancer Center | Trial completion date: Jan 2028 --> Mar 2029 | Trial primary completion date: Feb 2026 --> Apr 2027

One proposed mechanism for the development of both hematologic malignancies in this patient is the acquisition of a KMT2A rearrangement, raising the possibility of clonal evolution resulting in therapy-related or secondary leukemia. Another explanation is the presence of a common clonal stem cell progenitor harboring a JAK3 mutation.

P=N/A, N=153, Active, not recruiting, City of Hope Medical Center | Trial completion date: Dec 2025 --> Dec 2026

Continued studies evaluating JAK inhibitors in patients with T-PLL are warranted. This trial was registered at www.clinicaltrials.gov as #NCT03989466.

P1/2, N=36, Not yet recruiting, M.D. Anderson Cancer Center