Page 268 - Clinical Hematology_ Theory _ Procedures ( PDFDrive )

252 PART 4 ■ Erythrocyte Disorders

TABLE 13.4 Severe Congenital Neutropenia (SCN)

Hematologic Manifestation in

SCN Subtype Proposed Disease Mechanisms Addition to Severe Neutropenia

Mutated neutrophil elastase Unfolded protein response, excessive Leukemia predisposition

apoptosis of myeloid cells

Growth factor independent Defective transcription, myeloid Lymphopenia

transcription repressor 1 de ciency differentiation block

HAX-1 de ciency Mitochondrial leakage, excessive Leukemia predisposition

apoptosis

Glucose-6-phosphatase de ciency Impaired intracellular glucose Thrombocytopenia

(G-6-PD de ciency) homeostasis, excessive apoptosis

X-linked neutropenia Defective cytoskeleton organization, Lymphopenia

vesicle traf cking Leukemia predisposition

Vacuolar protein sorting-associated Defective lysosomal traf cking Myelo brosis

45 de ciency

Jagunal homolog 1 de ciency Aberrant N-glycosylation in biosynthetic Neutrophil dysfunction

pathway, reduced CDF3R signaling CSF3-hyporesponsiveness

Bi-allelic CSF3R de ciency Defective CSF3R signaling CSF3 unresponsiveness

Source: Touw IP. Game of clones: genomic evolution of severe congenital neutropenia. Hematology Am Soc Hematol Educ Program, December 5–8, 2015:1–6, 2015.

SCN , m , HAX- , m mm m F ’

X- k , z m m .
m m -m . I S m -D m m , m

T SCN . × m m k m
/L. P . . A .

I Staphylococcus aureus G m- L mm , m m m
m mm , - . m .

M SCN m - P m - -
- m (G-CSF, CSF ). G-CSF - m m (MDS)

m x SCN , m m k m (AML).
q m - P

m (MDS) m S m -D m m , f
m k m (AML). A q m m . Sk m

G-CSF mm m .
x m q m T m

G-CSF (CSF R). AML . M SBDS
m CSF R m , - %

m x m S m -D m m .
k m m m .

C m m
m SCN. I z CONGENI AL AMEGAKARYOCY IC

m m m HROMBOCY OPENIA
, - . C C m k m (CAM )

. I m m m
m m m x m

m MDS AML.
m ,

m k m . T
Schwachm an-Diam ond Syndrom e m k m

S m -D m m - m .

m , A m

m , , k m. I :