Outgrowth of a CSF3R-mutant clone drives a second myeloproliferative neoplasm in a chronic myeloid leukemia patient: a case report.

BACKGROUND: Chronic myeloid leukemia (CML) and chronic neutrophilic leukemia (CNL) are two myeloproliferative neoplasms with mutually exclusive diagnostic criteria. A hallmark of CML is the Philadelphia chromosome (Ph), which results in a BCR-ABL1 fusion gene and constitutive tyrosine kinase activity. CNL is a Ph-negative neoplasm and is defined in part by the presence of CSF3R mutations, which drive constative JAK/STAT signaling. CASE PRESENTATION: Here, we report the exceedingly rare co-occurrence of two granulocytic myeloproliferative neoplasms in a 69-year old male patient. After an initial diagnosis of chronic myeloid leukemia, the patient's clinical course was shaped by hematologic toxicity, the emergence of treatment-resistant BCR-ABL1 clones, and the expansion of a CSF3R-mutant clone without ABL1 mutations under selective pressure from tyrosine kinase inhibitors. The emergence of the CSF3R-mutant, neutrophilic clone led to the diagnosis of CNL as a second myeloproliferative neoplasm in the same patient. CONCLUSIONS: This is the first reported case of CNL arising subsequent to CML, which occurred under selective pressure from targeted therapy in a patient with complex clonal architecture. Patients with such molecularly complex disease may ultimately benefit from combination therapy that targets multiple oncogenic pathways.

Navigating Challenges in Monitoring Chronic Myeloid Leukemia with Multiple BCR-ABL1 Transcripts.

Quantitative PCR-based strategies are typically effective for monitoring BCR-ABL1 transcript levels in chronic myeloid leukemia (CML). Additionally, some patients treated with tyrosine kinase inhibitors can experience long-term treatment-free remission after discontinuation of the inhibitor. However, this outcome hinges on effectively monitoring the patient's response to therapy. We present a patient with CML and multiple BCR-ABL1 transcripts, including a rare isoform that lacks qPCR standardization. We describe unexpected discrepancies in transcript quantification, further having an impact on clinical decision-making regarding duration of treatment. To better inform clinical practice, we suggest monitoring patients at the same testing facility to better track transcript trend.

Maternal, Fetal, and Neonatal Imatinib Levels With Treatment of Chronic Myeloid Leukemia in Pregnancy.

BACKGROUND: Pregnant women with chronic myeloid leukemia (CML) can be treated effectively with the tyrosine-kinase inhibitor imatinib, but data regarding fetal and neonatal exposure and safety are limited. CASE: We present a patient with newly diagnosed CML in early pregnancy. Leukapheresis and interferon-α were initiated in the second trimester with limited benefit. Imatinib was subsequently started at 28 weeks of gestation with complete hematologic response within 4 weeks. No significant maternal or neonatal adverse effects were noted, but imatinib and its primary active metabolite concentrated in maternal breast milk and neonatal urine. CONCLUSION: Imatinib is effective for CML in pregnancy, but caution is warranted in light of potentially unrecognized fetal and neonatal effects.

Developmental changes in spinal motoneuron dendrites in neonatal mice.

We examined the age-dependent morphological changes of lumbar spinal motoneurons (MNs) in neonatal Swiss-Webster mice during the first 2 weeks of postnatal life. Neurons labeled by intracellular injection of biocytin in hemisected lumbosacral spinal cords in vitro were reconstructed from serial sections. Digitized data were compared for young (P3; postnatal days 2-4; n = 9) and older animals (P11; postnatal days 10-13; n = 8). As expected, measures of dendritic size (e.g., stem branch diameter, total surface area, maximum distance to tips, and lateral tree spread) were all significantly greater for P11 than for P3 mice. In contrast, the number of dendrites per MN and parameters related to tree topology (e.g., terminations per tree and maximum branch order), although slightly greater for P11 animals, were not significantly different between the two ages. Dendrite growth appeared to be proportional throughout the tree because the ratios between average terminal and internal branch lengths were similar for the two groups. Furthermore, this elongation was proportional to enlargement of overall spinal cord dimensions. A variety of other morphometric measures showed no significant difference between age groups. The relative constancy of MN dendritic topology up to P13 was surprising, given the striking maturation in motor function during this time period.